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1.
Am J Physiol Heart Circ Physiol ; 321(5): H976-H984, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34559578

RESUMO

Heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF) often arises from a prolonged LV pressure overload (LVPO) and accompanied by abnormal extracellular matrix (ECM) accumulation. The E3 ubiquitin ligase WWP1 is a fundamental determinant ECM turnover. We tested the hypothesis that genetic ablation of Wwp1 would alter the progression of LVPO-induced HFpEF. LV echocardiography in mice with global Wwp1 deletion (n = 23; Wwp1-/-) was performed at 12 wk of age (baseline) and then at 2 and 4 wk following LVPO (transverse aortic banding) or surgery without LVPO induction. Age-matched wild-type mice (Wwp1+/+; n = 23) underwent identical protocols. LV EF remained constant and unchanged with LVPO and LV mass increased in both groups but was lower in the Wwp1-/- mice. With LVPO, the E/A ratio, an index of LV filling, was 3.97 ± 0.46 in Wwp1+/+ but was 1.73 ± 0.19 in the Wwp1-/- group (P < 0.05). At the transcriptional level, mRNA for fibrillar collagens (types I and III) decreased by approximately 50% in Wwp1-/- compared with the Wwp1+/+ group at 4 wk post-LVPO (P < 0.05) and was paralleled by a similar difference in LV fibrillar collagen content as measured by histochemistry. Moreover, mRNA levels for determinants favoring ECM accumulation, such as transforming growth factor (TGF), increased with LVPO, but were lower in the Wwp1-/- group. The absence of Wwp1 reduced the development of left ventricular hypertrophy and subsequent progression to HFpEF. Modulating the WWP1 pathway could be a therapeutic target to alter the natural history of HFpEF.NEW & NOTEWORTHY Heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF) often arises from a prolonged LV pressure overload (LVPO) and is accompanied by abnormal extracellular matrix (ECM) accumulation. It is now recognized that the ECM is a dynamic entity that is regulated at multiple post-transcriptional levels, including the E3 ubiquitin ligases, such as WWP1. In the present study, WWP1 deletion in the context of an LVPO stimulus reduced functional indices of HFpEF progression and determinants of ECM remodeling.


Assuntos
Insuficiência Cardíaca/enzimologia , Ventrículos do Coração/enzimologia , Hipertrofia Ventricular Esquerda/enzimologia , Ubiquitina-Proteína Ligases/deficiência , Disfunção Ventricular Esquerda/enzimologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Diástole , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Deleção de Genes , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Tempo , Ubiquitina-Proteína Ligases/genética , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia
2.
Am J Physiol Heart Circ Physiol ; 321(5): H825-H838, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533401

RESUMO

Cardiovascular complications are the leading cause of death, and elevated levels of asymmetric dimethyarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are implicated in their pathophysiology. We investigated the role of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme hydrolyzing ADMA, in prevention of cardiovascular remodeling during hypertension. We hypothesized that the animals overexpressing DDAH1 will be protected from angiotensin II (ANG II)-induced end organ damage. Angiotensin II (ANG II) was infused in two doses: 0.75 and 1.5 mg/kg/day in DDAH1 transgenic mice (DDAH1 TG) and wild-type (WT) littermates for 2 or 4 wk. Echocardiography was performed in the first and fourth weeks of the infusion, systolic blood pressure (SBP) was measured weekly, and cardiac hypertrophy and vascular remodeling was assessed by histology. Increase in SBP after 1 wk of ANG II infusion was not different between the groups, whereas TG mice had lower SBP at later time points. TG mice were protected from cardiovascular remodeling after 2 wk of ANG II infusion in the high dose and after 4 wk in the moderate dose. TG mice had higher left ventricular lumen-to-wall ratio, lower cardiomyocyte cross-sectional area, and less interstitial fibrosis compared with WT controls. In aorta, TG mice had less adventitial fibrosis, lower medial thickness with preserved elastin content, lower counts of inflammatory cells, lower levels of active matrix metalloproteinase-2, and showed better endothelium-dependent relaxation. We demonstrated that overexpression of DDAH1 protects from ANG II-induced cardiovascular remodeling and progression of hypertension by preserving endothelial function and limiting inflammation.NEW & NOTEWORTHY We showed that overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects from angiotensin II-induced cardiovascular damage, progression of hypertension, and adverse vascular remodeling in vivo. This protective effect is associated with decreased levels of asymmetric dimethylarginine, preservation of endothelial function, inhibition of cardiovascular inflammation, and lower activity of matrix metalloproteinase-2. Our findings are highly clinically relevant, because they suggest that upregulation of DDAH1 might be a promising therapeutic approach against angiotensin II-induced end organ damage.


Assuntos
Amidoidrolases/biossíntese , Aorta/enzimologia , Pressão Sanguínea , Ventrículos do Coração/enzimologia , Hipertensão/enzimologia , Hipertrofia Ventricular Esquerda/enzimologia , Remodelação Vascular , Função Ventricular Esquerda , Remodelação Ventricular , Amidoidrolases/genética , Angiotensina II , Animais , Aorta/patologia , Aorta/fisiopatologia , Modelos Animais de Doenças , Indução Enzimática , Fibrose , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertensão/induzido quimicamente , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fatores de Tempo , Vasodilatação
3.
Am J Physiol Heart Circ Physiol ; 321(5): H940-H947, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34559582

RESUMO

Right-sided heart failure is a common consequence of pulmonary arterial hypertension. Overloading the right ventricle results in right ventricular hypertrophy, which progresses to failure in a process characterized by impaired Ca2+ dynamics and force production that is linked with transverse (t)-tubule remodeling. This also unloads the left ventricle, which consequently atrophies. Experimental left-ventricular unloading can result in t-tubule remodeling, but it is currently unclear if this occurs in right-sided heart failure. In this work, we used a model of monocrotaline (MCT)-induced right heart failure in male rats, using confocal microscopy to investigate cellular remodeling of t-tubules, junctophilin-2 (JPH2), and ryanodine receptor-2 (RyR2). We examined remodeling across tissue anatomical regions of both ventricles: in trabeculae, papillary muscles, and free walls. Our analyses revealed that MCT hearts demonstrated a significant loss of t-tubule periodicity, disruption of the normal sarcomere striated pattern with JPH2 labeling, and also a disorganized striated pattern of RyR2, a feature not previously reported in right heart failure. Remodeling of JPH2 and RyR2 in the MCT heart was more pronounced in papillary muscles and trabeculae compared with free walls, particularly in the left ventricle. We find that these structures, commonly used as ex vivo muscle preparations, are more sensitive to the disease process.NEW & NOTEWORTHY In this work, we demonstrate that t-tubule remodeling occurs in the atrophied left ventricle as well as the overloaded right ventricle after right-side heart failure. Moreover, we identify that t-tubule remodeling in both ventricles is linked to sarcoplasmic reticulum remodeling as indicated by decreased labeling periodicity of both the Ca2+ release channel, RyR2, and the cardiac junction-forming protein, JPH2, that forms a link between the sarcoplasmic reticulum and sarcolemma. Studies developing treatments for right-sided heart failure should consider effects on both the right and left ventricle.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Sarcômeros/patologia , Função Ventricular Esquerda , Função Ventricular Direita , Remodelação Ventricular , Animais , Sinalização do Cálcio , Modelos Animais de Doenças , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Monocrotalina , Ratos Wistar , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Sarcômeros/metabolismo
4.
Am J Physiol Heart Circ Physiol ; 321(5): H850-H864, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34477461

RESUMO

Molecular mechanisms underlying cardiac dysfunction and subsequent heart failure in diabetic cardiomyopathy are incompletely understood. Initially we intended to test the role of G protein-coupled receptor kinase 2 (GRK2), a potential mediator of cardiac dysfunction in diabetic cardiomyopathy, but found that control animals on HFD did not develop cardiomyopathy. Cardiac function was preserved in both wild-type and GRK2 knockout animals fed high-fat diet as indicated by preserved left ventricular ejection fraction (LVEF) although heart mass was increased. The absence of cardiac dysfunction led us to rigorously evaluate the utility of diet-induced obesity to model diabetic cardiomyopathy in mice. Using pure C57BL/6J animals and various diets formulated with different sources of fat-lard (32% saturated fat, 68% unsaturated fat) or hydrogenated coconut oil (95% saturated fat), we consistently observed left ventricular hypertrophy, preserved LVEF, and preserved contractility measured by invasive hemodynamics in animals fed high-fat diet. Gene expression patterns that characterize pathological hypertrophy were not induced, but a modest induction of various collagen isoforms and matrix metalloproteinases was observed in heart with high-fat diet feeding. PPARα-target genes that enhance lipid utilization such as Pdk4, CD36, AcadL, and Cpt1b were induced, but mitochondrial energetics was not impaired. These results suggest that although long-term fat feeding in mice induces cardiac hypertrophy and increases cardiac fatty acid metabolism, it may not be sufficient to activate pathological hypertrophic mechanisms that impair cardiac function or induce cardiac fibrosis. Thus, additional factors that are currently not understood may contribute to the cardiac abnormalities previously reported by many groups.NEW & NOTEWORTHY Dietary fat overload (DFO) is widely used to model diabetic cardiomyopathy but the utility of this model is controversial. We comprehensively characterized cardiac contractile and mitochondrial function in C57BL6/J mice fed with lard-based or saturated fat-enriched diets initiated at two ages. Despite cardiac hypertrophy, contractile and mitochondrial function is preserved, and molecular adaptations likely limit lipotoxicity. The resilience of these hearts to DFO underscores the need to develop robust alternative models of diabetic cardiomyopathy.


Assuntos
Cardiomiopatias Diabéticas/etiologia , Dieta Hiperlipídica , Hipertrofia Ventricular Esquerda/etiologia , Obesidade/complicações , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Fatores Etários , Animais , Cardiomiopatias Diabéticas/enzimologia , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Metabolismo Energético , Feminino , Fibrose , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertrofia Ventricular Esquerda/enzimologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/patologia , Miocárdio/enzimologia , Miocárdio/patologia , Disfunção Ventricular Esquerda/enzimologia , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Remodelação Ventricular
5.
Am J Physiol Heart Circ Physiol ; 321(4): H615-H632, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415186

RESUMO

Cardiac dysfunction in heart failure (HF) and diabetic cardiomyopathy (DCM) is associated with aberrant intracellular Ca2+ handling and impaired mitochondrial function accompanied with reduced mitochondrial calcium concentration (mito-[Ca2+]). Pharmacological or genetic facilitation of mito-Ca2+ uptake was shown to restore Ca2+ transient amplitude in DCM and HF, improving contractility. However, recent reports suggest that pharmacological enhancement of mito-Ca2+ uptake can exacerbate ryanodine receptor-mediated spontaneous sarcoplasmic reticulum (SR) Ca2+ release in ventricular myocytes (VMs) from diseased animals, increasing propensity to stress-induced ventricular tachyarrhythmia. To test whether chronic recovery of mito-[Ca2+] restores systolic Ca2+ release without adverse effects in diastole, we overexpressed mitochondrial Ca2+ uniporter (MCU) in VMs from male rat hearts with hypertrophy induced by thoracic aortic banding (TAB). Measurement of mito-[Ca2+] using genetic probe mtRCamp1h revealed that mito-[Ca2+] in TAB VMs paced at 2 Hz under ß-adrenergic stimulation is lower compared with shams. Adenoviral 2.5-fold MCU overexpression in TAB VMs fully restored mito-[Ca2+]. However, it failed to improve cytosolic Ca2+ handling and reduce proarrhythmic spontaneous Ca2+ waves. Furthermore, mitochondrial-targeted genetic probes MLS-HyPer7 and OMM-HyPer revealed a significant increase in emission of reactive oxygen species (ROS) in TAB VMs with 2.5-fold MCU overexpression. Conversely, 1.5-fold MCU overexpression in TABs, that led to partial restoration of mito-[Ca2+], reduced mitochondria-derived reactive oxygen species (mito-ROS) and spontaneous Ca2+ waves. Our findings emphasize the key role of elevated mito-ROS in disease-related proarrhythmic Ca2+ mishandling. These data establish nonlinear mito-[Ca2+]/mito-ROS relationship, whereby partial restoration of mito-[Ca2+] in diseased VMs is protective, whereas further enhancement of MCU-mediated Ca2+ uptake exacerbates damaging mito-ROS emission.NEW & NOTEWORTHY Defective intracellular Ca2+ homeostasis and aberrant mitochondrial function are common features in cardiac disease. Here, we directly compared potential benefits of mito-ROS scavenging and restoration of mito-Ca2+ uptake by overexpressing MCU in ventricular myocytes from hypertrophic rat hearts. Experiments using novel mito-ROS and Ca2+ biosensors demonstrated that mito-ROS scavenging rescued both cytosolic and mito-Ca2+ homeostasis, whereas moderate and high MCU overexpression demonstrated disparate effects on mito-ROS emission, with only a moderate increase in MCU being beneficial.


Assuntos
Arritmias Cardíacas/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Cálcio/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Técnicas Biossensoriais , Canais de Cálcio/genética , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Frequência Cardíaca , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Microscopia Confocal , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/patologia , Contração Miocárdica , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Regulação para Cima , Função Ventricular Esquerda , Remodelação Ventricular
7.
J Stroke Cerebrovasc Dis ; 30(9): 105946, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34214964

RESUMO

OBJECTIVES: Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. MATERIALS AND METHODS: This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. RESULTS: In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. CONCLUSIONS: Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).


Assuntos
Fibrilação Atrial/epidemiologia , Hemorragia Cerebral/epidemiologia , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Acidente Vascular Cerebral Lacunar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Diabetes Mellitus/epidemiologia , Progressão da Doença , Feminino , Frequência Cardíaca , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Itália/epidemiologia , Leucoencefalopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular
8.
Am Heart J ; 241: 83-86, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34302751

RESUMO

SARS-CoV-2 infection has been associated with cardiovascular disease in children, but which children need cardiac evaluation is unclear. We describe our experience evaluating 206 children for cardiac disease following SARS-CoV-2 infection (one of whom had ventricular ectopy) and propose a new guideline for management of these children. Routine cardiac screening after SARS-CoV-2 infection in children without any cardiac signs or symptoms does not appear to be high yield.


Assuntos
Assistência ao Convalescente , COVID-19/fisiopatologia , Cardiopatias/diagnóstico , Encaminhamento e Consulta , Adolescente , Assistência Ambulatorial , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Bradicardia/diagnóstico , Bradicardia/etiologia , Bradicardia/fisiopatologia , COVID-19/complicações , Cardiologia , Dor no Peito/fisiopatologia , Criança , Pré-Escolar , Dispneia/fisiopatologia , Ecocardiografia , Eletrocardiografia , Fadiga/fisiopatologia , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Direita/diagnóstico , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Ciência da Implementação , Masculino , Pediatria , Guias de Prática Clínica como Assunto , SARS-CoV-2 , Índice de Gravidade de Doença , Síncope/fisiopatologia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/etiologia , Complexos Ventriculares Prematuros/fisiopatologia , Adulto Jovem
9.
Nutr Metab Cardiovasc Dis ; 31(8): 2484-2489, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34088584

RESUMO

BACKGROUND AND AIMS: High waist circumference (WC) is associated with left ventricular mass index (LVMI) in childhood. However, no studies have assessed the association between WC change and left ventricular hypertrophy (LVH) in childhood. This study aimed to investigate the association between change in WC status over 2 years on LVH among Chinese children. METHODS AND RESULTS: Data were from a population-based prospective cohort study in China. Children without LVH at baseline (n = 1067) were assigned to four WC status change groups (persistent normal WC, WC loss, WC gain, and persistent abdominal obesity). Over a 2-year follow-up, 103 (out of 1067) children had LVH. LVMI levels were the highest among the persistent abdominal obesity group (31.5 ± 3.8 g/m 2.7), lower in the WC gain group (31.0 ± 3.6 g/m 2.7) and the WC loss group (29.8 ± 3.7 g/m 2.7), and lowest in the persistent normal WC group (29.1 ± 3.7 g/m 2.7). Compared with children in the persistent normal WC group, the odds of LVH was highest in the persistent abdominal obesity group [odds ratio (OR) = 3.57, 95% confidence interval (CI): 2.18-5.83], followed by the WC gain group (OR = 2.85, 95% CI: 1.50-5.41). In contrast, the odds of LVH was not increased in the WC loss group (OR = 0.93, 95% CI: 0.21-4.07). CONCLUSION: Although these findings highlight the importance of maintaining normal WC in childhood to reduce the odds of developing LVH, our data suggest the increased odds associated with abdominal obesity can be reversed by WC loss.


Assuntos
Hipertrofia Ventricular Esquerda/etiologia , Obesidade Abdominal/complicações , Obesidade Pediátrica/complicações , Função Ventricular Esquerda , Remodelação Ventricular , Circunferência da Cintura , Fatores Etários , Criança , China , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Masculino , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/terapia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/terapia , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Ganho de Peso , Perda de Peso
10.
Sci Rep ; 11(1): 13074, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158542

RESUMO

There is limited information on the association of body mass index (BMI) with left ventricular (LV) remodeling corresponding to severity of reduced lung function in patients with chronic obstructive pulmonary disease (COPD). Therefore, we investigated whether BMI is associated with cardiac atrial and ventricular dimensions according to severity of lung functional impairment in Chinese COPD elderly. A total of 563 hospitalized COPD patients with lung function impairment and 184 patients with non-COPD (aged 65-92 years) were collected retrospectively in a cross-sectional study in a university affiliated tertiary hospital in China. BMI and cardiac echocardiographic parameters were compared according to severity of lung functional impairment in COPD patients. BMI was 22.9 ± 3.9 kg/m2 in COPD patients, 24.0 ± 4.1 kg/m2 in non-COPD patients respectively. Reduced BMI, LV mass index, LV wall thickness and left atrial diameter, and dilated right ventricle (RV) existed in COPD patients with severe lung dysfunction as compared the COPD patients with mild to moderate lung functional reduction and non-COPD patients (P < 0.05), while there were no differences in BMI and echocardiographic parameters between the COPD patients with mild to moderate lung functional decline and non-COPD patients (P > 0.05). Logistic regression analysis showed that low BMI (BMI < 18.5 kg/m2) was correlated with reduced LV mass and wall thickness, dilated RV and reduced lung function in the COPD patients with severe lung dysfunction. In conclusion, this study demonstrates that lower BMI is associated not only with dilated RV and impaired pulmonary function, but also it is related to reduced LV mass in Asian COPD elderly with severe lung dysfunction.


Assuntos
Peso Corporal/fisiologia , Ventrículos do Coração/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Ecocardiografia , Ecocardiografia Doppler/métodos , Feminino , Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Pulmão/fisiopatologia , Masculino , Estudos Retrospectivos , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular
11.
J Am Heart Assoc ; 10(13): e019995, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34169737

RESUMO

Background Inhibitors of the sodium-glucose linked transporter 2 improve cardiovascular outcomes in patients with or without type 2 diabetes mellitus, but the effects on cardiac energetics and mitochondrial function are unknown. We assessed the effects of sodium-glucose linked transporter 2 inhibition on mitochondrial function, high-energy phosphates, and genes encoding mitochondrial proteins in hearts of mice with and without diet-induced diabetic cardiomyopathy. Methods and Results Mice fed a control diet or a high-fat, high-sucrose diet received ertugliflozin mixed with the diet (0.5 mg/g of diet) for 4 months. Isolated mitochondria were assessed for functional capacity. High-energy phosphates were assessed by 31P nuclear magnetic resonance spectroscopy concurrently with contractile performance in isolated beating hearts. The high-fat, high-sucrose diet caused myocardial hypertrophy, diastolic dysfunction, mitochondrial dysfunction, and impaired energetic response, all of which were prevented by ertugliflozin. With both diets, ertugliflozin caused supernormalization of contractile reserve, as measured by rate×pressure product at high work demand. Likewise, the myocardial gene sets most enriched by ertugliflozin were for oxidative phosphorylation and fatty acid metabolism, both of which were enriched independent of diet. Conclusions Ertugliflozin not only prevented high-fat, high-sucrose-induced pathological cardiac remodeling, but improved contractile reserve and induced the expression of oxidative phosphorylation and fatty acid metabolism gene sets independent of diabetic status. These effects of sodium-glucose linked transporter 2 inhibition on cardiac energetics and metabolism may contribute to improved structure and function in cardiac diseases associated with mitochondrial dysfunction, such as heart failure.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Metabolismo Energético/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/prevenção & controle , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Disfunção Ventricular Esquerda/prevenção & controle , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Dieta Hiperlipídica , Sacarose na Dieta , Metabolismo Energético/genética , Regulação da Expressão Gênica , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
12.
Open Heart ; 8(1)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34158367

RESUMO

BACKGROUND: The criteria to define the grade of aortic stenosis (AS)-aortic valve area (AVA) and mean gradient (MG) or peak jet velocity-do not always coincide into one grade. Although in severe AS, this discrepancy is well characterised, in moderate AS, the phenomenon of discordant grading has not been investigated and its prognostic implications are unknown. OBJECTIVES: To investigate the occurrence of discordant grading in patients with moderate AS (defined by an AVA between 1.0 cm² and 1.5 cm² but with an MG <20 mm Hg) and how these patients compare with those with concordant grading moderate AS (AVA between 1.0 cm² and 1.5 cm² and MG ≥20 mm Hg) in terms of clinical outcomes. METHODS: From an ongoing registry of patients with AS, patients with moderate AS based on AVA were selected and classified into discordant or concordant grading (MG <20 mm Hg or ≥20 mm Hg, respectively). The clinical endpoint was all-cause mortality. RESULTS: Of 790 patients with moderate AS, 150 (19.0%) had discordant grading, moderate AS. Patients with discordant grading were older, had higher prevalence of previous myocardial infarction and left ventricular (LV) hypertrophy, larger LV end-diastolic and end-systolic volume index, higher LV filling pressure and lower LV ejection fraction and stroke volume index as compared with their counterparts. After a median follow-up of 4.9 years (IQR 3.0-8.2), patients with discordant grading had lower aortic valve replacement rates (26.7% vs 44.1%, p<0.001) and higher mortality rates (60.0% vs 43.1%, p<0.001) as compared with patients with concordant grading. Discordant grading moderate AS, combined with low LV ejection fraction, presented the higher risk of mortality (HR 2.78 (2.00-3.87), p<0.001). CONCLUSION: Discordant-grading moderate AS is not uncommon and, when combined with low LV ejection fraction, is associated with high risk of mortality.


Assuntos
Estenose da Valva Aórtica/diagnóstico , Valva Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Hipertrofia Ventricular Esquerda/etiologia , Sistema de Registros , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Prognóstico , Índice de Gravidade de Doença
13.
Sci Rep ; 11(1): 13022, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158575

RESUMO

Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of obesity on prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction in children. In this analysis of prospectively collected cross-sectional data of children between 5 and 16 years of age from randomly selected schools in Peru, parameters of LV geometry and function were compared according to presence or absence of obesity (body mass index z-score > 2). LVH was based on left ventricular mass index (LVMI) adjusted for age and sex and defined by a z-score of > 2. LV diastolic function was assessed using mitral inflow early-to-late diastolic flow (E/A) ratio, peak early diastolic tissue velocities of the lateral mitral annulus (E'), early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity (E/E') ratio, and left atrial volume index (LAVI). Among 1023 children, 681 children (mean age 12.2 ± 3.1 years, 341 male (50.1%)) were available for the present analysis, of which 150 (22.0%) were obese. LVH was found in 21 (14.0%) obese and in 19 (3.6%) non-obese children (padjusted < 0.001). LVMI was greater in obese than that in non-obese children (36.1 ± 8.6 versus 28.7 ± 6.9 g/m2.7, p < 0.001). The mean mitral E/E' ratio and LAVI were significantly higher in obese than those in non-obese individuals (E/E': 5.2 ± 1.1 versus 4.9 ± 0.8, padjusted = 0.043; LAVI 11.0 ± 3.2 versus 9.6 ± 2.9, padjusted = 0.001), whereas E' and E/A ratio were comparable. Childhood obesity was associated with left ventricular hypertrophy and determinants of diastolic dysfunction.ClinicalTrials.gov Identifier: NCT02353663.


Assuntos
Diástole/fisiologia , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Adolescente , Índice de Massa Corporal , Criança , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/patologia , Masculino , Miocárdio/patologia , Obesidade/patologia , Tamanho do Órgão
14.
Front Immunol ; 12: 670153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135897

RESUMO

Background: Myocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABAA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABAA receptor-mediated macrophage responses in pressure overload-induced heart failure. Methods and Results: C57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABAA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABAA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6Clow macrophages in the heart during POH and circulating Ly6Chigh classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6Clow macrophages toward MHCIIhigh macrophage polarization. As a result, Ly6Clow macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6ClowMHCIIhigh macrophage polarization increased expression levels of osteopontin and TGF-ß, which led to myocardial hypertrophy and fibrosis. Conversely, GABAA receptor blockage with bicuculline reversed these effects. Conclusions: Control of the GABAA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABAA receptor has the potential to improve pressure overload-induced heart failure.


Assuntos
Antagonistas de Receptores de GABA-A/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Pressão Arterial , Modelos Animais de Doenças , Fibrose , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Ligadura , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Receptores de GABA-A/metabolismo , Transdução de Sinais , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
15.
Sci Rep ; 11(1): 11516, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075174

RESUMO

Recently, a new ECG criterion, the Peguero-Lo Presti (PLP), improved overall accuracy in the diagnosis of left ventricular hypertrophy (LVH)-compared to traditional ECG criteria, but with few patients with advanced age. We analyzed patients with older age and examined which ECG criteria would have better overall performance. A total of 592 patients were included (83.1% with hypertension, mean age of 77.5 years) and the PLP criterion was compared against Cornell voltage (CV), Sokolow-Lyon voltage (SL) and Romhilt-Estes criteria (cutoffs of 4 and 5 points, RE4 and RE5, respectively) using LVH defined by the echocardiogram as the gold standard. The PLP had higher AUC than the CV, RE and SL (respectively, 0.70 vs 0.66 vs 0.64 vs 0.67), increased sensitivity compared with the SL, CV and RE5 (respectively, 51.9% [95% CI 45.4-58.3%] vs 28.2% [95% CI 22.6-34.4%], p < 0.0001; vs 35.3% [95% CI 29.2-41.7%], p < 0.0001; vs 44.4% [95% CI 38.0-50.9%], p = 0.042), highest F1 score (58.3%) and net benefit for most of the 20-60% threshold range in the decision curve analysis. Overall, despite the best diagnostic performance in older patients, the PLP criterion cannot rule out LVH consistently but can potentially be used to guide clinical decision for echocardiogram ordering in low-resource settings.


Assuntos
Eletrocardiografia , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
16.
Sci Rep ; 11(1): 12411, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127728

RESUMO

Atrial fibrillation (AF) leads to remodeling characterized by changes in both size and shape of the left atrium (LA). Here we aimed to study the effect of hypertrophic cardiomyopathy (HCM) on the pattern of LA remodeling in AF-patients. HCM-patients (n = 23) undergoing AF ablation (2009-2012) were matched and compared with 125 Non-HCM patients from our prospective registry. Pre-procedural CT data were analyzed (EnSite Verismo, SJM, MN) to determine the maximal sagittal (anterior-posterior, AP), coronal (superior-inferior, SI and transversal, TV) dimensions and the sphericity index (LAS). Volume (LAV) was rendered after appendage (LAA) and pulmonary vein (PV) exclusion. A cutting plane, between PV ostia/LAA and parallel to the posterior wall, divided LAV into anterior- (LA-A) and posterior-LA (LA-P) parts. The ratio LA-A/LAV was defined as asymmetry index (ASI). HCM patients had a wider inter-ventricular septum and a smaller LV than Non-HCM patients. LA volume (LAV 166 ± 72 vs. 130 ± 36 ml, p = 0.03) and LA diameters were significantly larger in HCM patients. Anterior volume (LA-A: 112 ± 48 vs. 83 ± 26 ml, p < 0.001) differed significantly between groups, whereas the posterior volume LA-P (55 ± 28 vs. 47 ± 13 ml, p = 0.23) and LAS (75% vs. 78%, p = 0.089) was similar in both groups. As a result, ASI was significantly higher (67 ± 6 vs. 63 ± 6%, p = 0.01) in HCM than in Non-HCM patients. In conclusion, LA remodeling in patients with AF and HCM is characterized by asymmetric dilatation, driven by an anterior rather than a posterior dilatation. This can be characterized by three-dimensional imaging and could be used as surrogate of advanced atrial remodeling.


Assuntos
Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Cardiomiopatia Hipertrófica/complicações , Átrios do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/complicações , Idoso , Fibrilação Atrial/etiologia , Fibrilação Atrial/cirurgia , Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/fisiopatologia , Ablação por Cateter , Ecocardiografia , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Prevalência , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
High Blood Press Cardiovasc Prev ; 28(4): 383-391, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33950510

RESUMO

INTRODUCTION: Hypertensive mediated heart disease is the consequence of anatomical and functional changes in cardiovascular system. The benefits on left ventricular (LV) diastolic impairment and remodeling of hypertension treatment are well established. AIM: To evaluate LV structure, systolic and diastolic function of treated hypertensive patients on a medium to long term follow-up. METHODS: Prospectively observational cohort study. Hypertensive patients over 18 years, ultrasound evaluation of LV structure and diastolic and systolic function, follow-up at least once a year. Diastolic function assessed following recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. RESULTS: 285 patients, mean follow up of 1731 ± 952 days. Sample mean age 56.3 ± 12.5 years, 166 patients (58.3%) were males. Baseline blood pressure 147.8 ± 19/86.8 ± 11 mm Hg, 5 years blood pressure 134.4 ± 15.7/79 ± 9 mm Hg (p < 0.005 SBP and p < 0.01 DBP). Baseline fixed dose combinations 115 patients (40.4%), follow-up 53.1% (p < 0.05). LV remodeling was detected in 88 patients (30.9%) vs. 30.1% at 5 years (p = NS). The frequency of an E/e' ratio > 14 was reduced from 38 patients (13.3%) to 3.6% (p < 0.001), e' septal velocity < 7 cm/sec or e' lateral velocity < 10 cm/sec was reduced from 38.6% (110 patients) to 19.3% (p < 0.001). Baseline normal diastolic function was detected in 85.6% (244 patients) and 94% at the end of the follow-up (p < 0.02). CONCLUSIONS: In this observational cohort followed by a mean of 5 years, the main benefit of hypertension treatment was the prevention or regression of diastolic dysfunction.


Assuntos
Anti-Hipertensivos/uso terapêutico , Cardiopatias/etiologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Diástole/efeitos dos fármacos , Feminino , Seguimentos , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sístole/efeitos dos fármacos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle
19.
BMC Cardiovasc Disord ; 21(1): 187, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858344

RESUMO

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD. METHODS: A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing < 50%) on CCTA were included in the study. The major exclusion criteria were structural heart disease and a history of myocardial infarction or coronary revascularization. Abnormal LV geometry on echocardiography was defined as LV mass index > 95 g/m2 in women and > 115 g/m2 in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality. RESULTS: A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p < 0.001). After adjustment for confounding factors, abnormal LV geometry was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.64; 95% confidence interval, 1.04-2.58; p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p < 0.001). CONCLUSIONS: Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/mortalidade , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul , Fatores de Tempo
20.
BMC Cardiovasc Disord ; 21(1): 194, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879070

RESUMO

BACKGROUND: Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. METHODS: CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. RESULTS: We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. CONCLUSIONS: Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Irbesartana/farmacologia , Monócitos/efeitos dos fármacos , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Interleucina-10/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Monócitos/metabolismo , Fenótipo , Receptores de Superfície Celular/sangue , Receptores Imunológicos/sangue , Fator de Necrose Tumoral alfa/sangue , Função Ventricular Esquerda , Remodelação Ventricular
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