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1.
Int J Sports Med ; 41(1): 27-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791086

RESUMO

Several athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.


Assuntos
Futebol Americano/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Remodelação Ventricular/fisiologia , Adolescente , Afro-Americanos , Composição Corporal/fisiologia , Ecocardiografia , Grupo com Ancestrais do Continente Europeu , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Fatores Raciais , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
2.
Angiology ; 71(1): 70-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31446774

RESUMO

Both elevated resting heart rate (HR) and electrocardiographic left ventricular hypertrophy (ECG-LVH) are signs of a poor prognosis. Although elevated resting HR is a known risk factor for cardiovascular disease and target organ damage, the association between resting HR and the development of ECG-LVH is unclear. In the present study, 6860 subjects (4203 men, 2657 women, 19-89 years of age) without ECG-LVH at baseline were evaluated and followed for a mean duration of 3.7±1.4 years. During the follow-up period, 484 (7.1%) subjects developed ECG-LVH. Cox regression analysis revealed that each 10 beats/min increase in resting HR was associated with a 22% reduction in the development of ECG-LVH (95% confidence interval: 12%-30%, P < .0001) in men. While an increase in HR tended to be associated with the development of ECG-LVH in women, the relationship was not significant. In contrast to the concept that an elevated resting HR is a cardiovascular risk factor, these findings revealed that resting HR was negatively associated with the development of ECG-LVH in men.


Assuntos
Frequência Cardíaca , Hipertrofia Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Eletrocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
3.
Toxicol Lett ; 318: 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31585160

RESUMO

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.


Assuntos
Antineoplásicos/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Inseticidas/toxicidade , Piruvatos/toxicidade , Rotenona/toxicidade , Taquicardia Ventricular/induzido quimicamente , Fibrilação Ventricular/induzido quimicamente , Remodelação Ventricular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Conexina 43/genética , Conexina 43/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/ultraestrutura , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ratos Wistar , Período Refratário Eletrofisiológico/efeitos dos fármacos , Medição de Risco , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologia
4.
Cell Physiol Biochem ; 53(6): 961-981, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31820856

RESUMO

BACKGROUND/AIMS: We assessed the effects of ticagrelor, aspirin and prasugrel, started 7days after myocardial ischemia-reperfusion injury on remodeling, inflammation and fibrosis in the rat. We examined whether ticagrelor can affect the number of progenitor cells in the border zone. Ticagrelor, started 24h after myocardial ischemia-reperfusion injury, attenuates the decrease in heart function and adverse remodeling, an effect which is blocked by aspirin. METHODS: Rats underwent 40min ischemia followed by reperfusion. Oral dosing with vehicle, ticagrelor (300mg/kg/d), aspirin (20mg/kg/d), their combination or prasugrel (15mg/kg/d) started 7days after infarction. Echocardiography was used to assess systolic function. Heart tissue were analyzed by rt-PCR, immunoblotting, ELISA and immunohistochemistry 2weeks after infarction. RESULTS: Both ticagrelor and aspirin attenuated the decrease in systolic function and remodeling, an effect that was blocked by their combination. Ticagrelor and aspirin attenuated the increase in ANP, BNP, collagen-I and collagen-III. Again, the effect was blocked by their combination. Ticagrelor increased c-Kit, Sca-1, Ki-67, CD34, attenuated the decrease in CD105 mRNA levels, and attenuated the increase in CD31, whereas aspirin increased Ki-67, suppressed the increase in CD31 and attenuated the decrease in CD105 mRNA levels. Prasugrel did not display any effects. CONCLUSION: Ticagrelor attenuated adverse remodeling and deterioration of left ventricular systolic function despite starting treatment after the myocardial ischemia-reperfusion injury is completed. Aspirin had similar effects; however, when combined with ticagrelor, the protective effects were significantly attenuated. Ticagrelor increased the levels of several markers of stem cells and regeneration, suggesting cardiac healing by recruiting regenerative cells into the infarct.


Assuntos
Apoptose/efeitos dos fármacos , Infarto do Miocárdio/patologia , Inibidores da Agregação de Plaquetas/farmacologia , Ticagrelor/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Aspirina/farmacologia , Aspirina/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Endoglina/genética , Endoglina/metabolismo , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/farmacologia , Cloridrato de Prasugrel/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Ticagrelor/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos
5.
Vasc Health Risk Manag ; 15: 539-550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827327

RESUMO

Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
7.
Kardiologiia ; 59(12): 84-91, 2019 Dec 11.
Artigo em Russo | MEDLINE | ID: mdl-31849315

RESUMO

Chronic heart failure (CHF) remains one of the most important problems of modern cardiology. One of the effective treatment methods is resynchronization therapy (RT). The article presents an analysis of literature data on the effectiveness of RT in improving the quality of life, reducing the number of hospitalizations and mortality in patients with heart failure with severe left ventricular systolic dysfunction and expanding QRS complex, and also discusses key methods for optimizing RT.


Assuntos
Insuficiência Cardíaca , Terapia de Ressincronização Cardíaca , Doença Crônica , Humanos , Qualidade de Vida , Disfunção Ventricular Esquerda , Remodelação Ventricular
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(10): 1049-1054, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31642443

RESUMO

OBJECTIVE: To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice. METHODS: A total of 54 FVB/N mice were randomly divided into 4 groups: 0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group. RESULTS: There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P<0.05). There were no significant changes in HW/TL ratio and dLVPW from days 14 to 21 of ISO injection (P>0.05), while there was a significant reduction in myocardial fiber diameter (P<0.05), which was similar to the value on day 7 (P>0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P<0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection. CONCLUSIONS: The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.


Assuntos
Remodelação Ventricular , Animais , Isoproterenol , MAP Quinase Quinase Quinase 5 , Camundongos , Miocárdio , Miócitos Cardíacos
9.
Kardiologiia ; 59(9S): 16-24, 2019 Sep 11.
Artigo em Russo | MEDLINE | ID: mdl-31644413

RESUMO

Left ventricular hypertrophy - is one of the most frequent structural changes in the heart. This article is devoted to the assessment of modern views on the causes of myocardial hypertrophy of the donor heart, indications and contraindications for the heart trans­ plantation, the outlook of expanding the pool of effective donors through the use of these hearts. Here are considered the issues of post-transplantation remodeling of the donor heart myocardium, The pathogenesis features, the nascence risk and possibilities of drug regulation of the transplanted heart's myocardial hypertrophy of the left ventricle.


Assuntos
Transplante de Coração , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda , Humanos , Miocárdio , Doadores de Tecidos , Remodelação Ventricular
10.
Acta Cir Bras ; 34(8): e201900807, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618407

RESUMO

PURPOSE: To investigate the effect of tanshinone IIA (TIIA) on ventricular remodeling in rats with pressure overload-induced heart failure. METHODS: Pressure overload-induced heart failure model (abdominal aortic coarctation) was established in 40 rats, which were divided into model and 5, 10 and 20 mg/kg TIIA groups. Ten rats receiving laparotomy excepting abdominal aortic coarctation were enrolled in sham-operated group. The 5, 10 and 20 mg/kg TIIA groups were treated with 5, 10 and 20 mg/kg TIIA, respectively, for 8 weeks. RESULTS: Compared with model group, in 20 mg/kg TIIA group the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, ±maximum left ventricular pressure rising and dropping rate, and myocardial B-cell lymphoma-2 and cleaved cysteinyl aspartate specific proteinase-3 protein levels were increased, respectively (P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic pressure, heart weight index, left ventricular weight index, serum B-type brain natriuretic peptide, interleukin 6 and C-reactive protein levels and myocardial B-cell lymphoma-2 associated X protein level were decreased, respectively (P<0.05). CONCLUSION: TIIA may alleviate ventricular remodeling in rats with pressure overload-induced heart failure heart by reducing inflammatory response and cardiomyocyte apoptosis.


Assuntos
/farmacologia , Insuficiência Cardíaca/fisiopatologia , Coração/efeitos dos fármacos , Imunossupressores/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ventrículos do Coração/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Pressão Ventricular
11.
Life Sci ; 238: 116974, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639399

RESUMO

AIM: Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility and intracellular Ca2+ transient in rats with MCT-induced PAH. MAIN METHODS: Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes. KEY FINDINGS: Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes. SIGNIFICANCE: Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.


Assuntos
Insuficiência Cardíaca/prevenção & controle , Hipertensão Pulmonar/complicações , Hipertrofia Ventricular Direita/prevenção & controle , Contração Muscular , Miócitos Cardíacos/patologia , Condicionamento Físico Animal , Artéria Pulmonar/patologia , Remodelação Ventricular , Animais , Cálcio , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/patologia , Masculino , Ratos , Ratos Wistar , Corrida
12.
Kardiologiia ; 59(9): 71-82, 2019 Sep 17.
Artigo em Russo | MEDLINE | ID: mdl-31540578

RESUMO

In this article we present discussion of the current state of the problem of surgical treatment of ischemic cardiomyopathy (ICM). The pathophysiological aspects of left ventricular remodeling in patients with ICM are also covered. A detailed characterization of methods for assessing the myocardial viability is given and their role in patients with ICM is shown. The problem of right ventricular dysfunction in ICM is discussed. Main attention is focused on the methods of surgical treatment of ICM. Limitations of the Surgical Treatment for Ischemic Heart Failure (STICH) study are analyzed. The article is intended for cardiologists, general practitioners and cardiac surgeons.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Miocárdio , Remodelação Ventricular
13.
Int Heart J ; 60(5): 1168-1175, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484876

RESUMO

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.


Assuntos
Conexina 43/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Neprilisina/farmacologia , Taquicardia Ventricular/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Biópsia por Agulha , China , Modelos Animais de Doenças , Ecocardiografia/métodos , Imuno-Histoquímica , Masculino , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Taxa de Sobrevida , Sistema Nervoso Simpático/efeitos dos fármacos , Taquicardia Ventricular/diagnóstico por imagem
14.
EBioMedicine ; 46: 236-247, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31401194

RESUMO

BACKGROUND: Myocardial infarction (MI) is a life-threatening disease, often leading to heart failure. Defining therapeutic targets at an early time point is important to prevent heart failure. METHODS: MicroRNA screening was performed at early time points after MI using paired samples isolated from the infarcted and remote myocardium of pigs. We also examined the microRNA expression in plasma of MI patients and pigs. For mechanistic studies, AAV9-mediated microRNA knockdown and overexpression were administrated in mice undergoing MI. FINDINGS: MicroRNAs let-7a and let-7f were significantly downregulated in the infarct area within 24 h post-MI in pigs. We also observed a reduction of let-7a and let-7f in plasma of MI patients and pigs. Inhibition of let-7 exacerbated cardiomyocyte apoptosis, induced a cardiac hypertrophic phenotype, and resulted in worsened left ventricular ejection fraction. In contrast, ectopic let-7 overexpression significantly reduced those phenotypes and improved heart function. We then identified TGFBR3 as a target of let-7, and found that induction of Tgfbr3 in cardiomyocytes caused apoptosis, likely through p38 MAPK activation. Finally, we showed that the plasma TGFBR3 level was elevated after MI in plasma of MI patients and pigs. INTERPRETATION: Together, we conclude that the let-7-Tgfbr3-p38 MAPK signalling plays an important role in cardiomyocyte apoptosis after MI. Furthermore, microRNA let-7 and Tgfbr3 may serve as therapeutic targets and biomarkers for myocardial damage. FUND: Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis, Thematic Research Program and the Summit Research Program, Taiwan.


Assuntos
Apoptose/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Proteoglicanas/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Modelos Animais de Doenças , Ecocardiografia , Terapia Genética/métodos , Vetores Genéticos/genética , Humanos , Camundongos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Suínos , Fatores de Tempo , Transdução Genética , Remodelação Ventricular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Int J Cardiovasc Imaging ; 35(11): 2057-2065, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402413

RESUMO

This study was aimed to investigate the correlation between left ventricular (LV) myocardial strain and LV geometry in healthy adults using cardiovascular magnetic resonance-feature tracking (CMR-FT). 124 gender-matched healthy adults who underwent healthy checkup using CMR cine imaging were retrospectively analyzed. Peak global radial, circumferential, longitudinal strain (GRS, GCS and GLS) for left ventricle were measured. LV geometry was assessed by the ratio of LV mass (LVM) and end-diastolic volume (EDV). GRS, GCS and GLS were 34.18 ± 6.71%, - 22.17 ± 2.28%, - 14.76 ± 2.39% for men, and 33.40 ± 6.95%, - 22.49 ± 2.27%, - 15.72 ± 2.36% for women. Multiple linear regression showed that LVM/EDV was associated with decreased GLS (ß = - 0.297, p = 0.005), but was not significantly associated with GRS and GCS (both p > 0.05). There was an increase in the magnitude of GRS, GCS and GLS with advancing age (ß = 0.254, ß = 0.466 and ß = 0.313, all p < 0.05). Greater BMI was associated with decreased GRS, GCS and GLS (ß = - 0.232, ß = - 0. 249 and ß = - 0.279, all p < 0.05). In conclusion, compared with GRS and GCS, GLS is more sensitive to assess LV concentric remodeling in healthy adults. GRS, GCS and GLS are all independently positively associated with age and negatively associated with BMI. Sex-based LV strain reference values for healthy Chinese adults are established.


Assuntos
Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Contração Miocárdica , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores Sexuais
16.
Int J Mol Sci ; 20(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398927

RESUMO

Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water-salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.


Assuntos
Sistema Cardiovascular/metabolismo , Peptídeos Natriuréticos/metabolismo , Animais , Sistema Cardiovascular/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Peptídeo Natriurético Encefálico/farmacologia , Peptídeos Natriuréticos/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Remodelação Vascular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
19.
Int J Mol Sci ; 20(16)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434314

RESUMO

Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/patologia , Fibrose/patologia , MicroRNAs/metabolismo , Biomarcadores/química , Cardiomiopatia Chagásica/genética , Feminino , Fibrose/genética , Fibrose/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Remodelação Ventricular/genética , Remodelação Ventricular/fisiologia
20.
Int J Mol Sci ; 20(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416126

RESUMO

Mice bearing targeted gene mutations that affect the functions of natriuretic peptides (NPs) and natriuretic peptide receptors (NPRs) have contributed important information on the pathogenesis of hypertension, kidney disease, and cardiovascular dysfunction. Studies of mice having both complete gene disruption and tissue-specific gene ablation have contributed to our understanding of hypertension and cardiovascular disorders. These phenomena are consistent with an oligogenic inheritance in which interactions among a few alleles may account for genetic susceptibility to hypertension, renal insufficiency, and congestive heart failure. In addition to gene knockouts conferring increased risks of hypertension, kidney disorders, and cardiovascular dysfunction, studies of gene duplications have identified mutations that protect against high blood pressure and cardiovascular events, thus generating the notion that certain alleles can confer resistance to hypertension and heart disease. This review focuses on the intriguing phenotypes of Npr1 gene disruption and gene duplication in mice, with emphasis on hypertension and cardiovascular events using mouse models carrying Npr1 gene knockout and/or gene duplication. It also describes how Npr1 gene targeting in mice has contributed to our knowledge of the roles of NPs and NPRs in dose-dependently regulating hypertension and cardiovascular events.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Variação Genética , Guanilato Ciclase/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Animais , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Duplicação Gênica , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/metabolismo , Camundongos , Polimorfismo Genético , Disfunção Ventricular Esquerda , Remodelação Ventricular
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