Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.843
Filtrar
1.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066865

RESUMO

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-ß and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose , Cardiotônicos/uso terapêutico , Hipertensão Maligna/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cardiotônicos/farmacologia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Maligna/enzimologia , Hipertensão Maligna/patologia , Hipertensão Maligna/fisiopatologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Miocárdio/patologia , NG-Nitroarginina Metil Éster/química , NG-Nitroarginina Metil Éster/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Ratos Endogâmicos SHR , Resveratrol/química , Resveratrol/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Proteína X Associada a bcl-2/metabolismo
2.
Pan Afr Med J ; 38: 192, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1206456

RESUMO

COVID-19 infection is responsible for many complications, which can lead to a high risk of mortality in some patients. Among them are cardiovascular complications which are classified as the most severe. We report a case of a young woman, with no relevant pathological history, admitted for COVID-19 infection, complicated by myocarditis with severe ventricular dysfunction, cardiogenic shock and a large thrombosis into the left ventricle (LV) that was responsible for a left lower limb ischemia associated with a deep venous thrombosis of right lower limb.


Assuntos
COVID-19/complicações , Miocardite/virologia , Choque Cardiogênico/virologia , Trombose/virologia , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/virologia , Humanos , Isquemia/etiologia , Extremidade Inferior/irrigação sanguínea , Pessoa de Meia-Idade , Trombose Venosa/virologia
3.
Nat Commun ; 12(1): 3155, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039977

RESUMO

Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.


Assuntos
Técnicas de Cultura de Células/métodos , Insuficiência Cardíaca/terapia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/transplante , Células-Tronco Pluripotentes/fisiologia , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Modelos Animais de Doenças , Embrião de Mamíferos , Desenvolvimento Embrionário/fisiologia , Átrios do Coração/citologia , Átrios do Coração/embriologia , Insuficiência Cardíaca/patologia , Ventrículos do Coração/citologia , Ventrículos do Coração/embriologia , Ventrículos do Coração/patologia , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Ratos
4.
Pan Afr Med J ; 38: 192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995798

RESUMO

COVID-19 infection is responsible for many complications, which can lead to a high risk of mortality in some patients. Among them are cardiovascular complications which are classified as the most severe. We report a case of a young woman, with no relevant pathological history, admitted for COVID-19 infection, complicated by myocarditis with severe ventricular dysfunction, cardiogenic shock and a large thrombosis into the left ventricle (LV) that was responsible for a left lower limb ischemia associated with a deep venous thrombosis of right lower limb.


Assuntos
COVID-19/complicações , Miocardite/virologia , Choque Cardiogênico/virologia , Trombose/virologia , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/virologia , Humanos , Isquemia/etiologia , Extremidade Inferior/irrigação sanguínea , Pessoa de Meia-Idade , Trombose Venosa/virologia
5.
Biomed Res Int ; 2021: 2043415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33969115

RESUMO

The protective effect of aspirin against myocardial hypertrophy (MH) was studied. Model rats of pressure overload MH were prepared by abdominal aortic coarctation. Rats were randomly divided into the sham group (n = 9), MH model group (n = 9), and MH+aspirin group (n = 9), which was, respectively, divided into the 4-week group and 8-week group according to the time of intragastric administration. Arterial blood pressure and left ventricular mass index (LVMI) were measured. Changes in myocardial tissue structure were observed by HE staining, Masson staining, and reticular fiber staining. Cardiomyocyte apoptosis was detected by TUNEL assay. The levels of TNF-α, IL-10, TXA2, and PGI2 in myocardium and plasma were detected by ELISA. The arterial blood pressure in the MH model group was significantly higher than that in the 4- and 8-week sham groups, but that in the MH+aspirin group was significantly lower than that in the MH model group. At 4 and 8 weeks, the LVWI in the MH model group was significantly higher than that in the sham group, but it was significantly reduced after aspirin treatment. The myocardial cell hypertrophy was obvious, collagen fibers were proliferated, and reticular fibers were reduced in the 4- and 8-week MH model groups. Compared with the MH model groups, myocardial cells in the MH+aspirin groups were significantly reduced, the collagen fiber content was significantly reduced, and the reticular fiber content was increased. The apoptotic cardiomyocytes in the 4- and 8-week MH model groups were obviously increased. The apoptosis of myocardial cells in the MH+aspirin groups was obviously decreased. The TNF-α levels in the myocardial tissue of the 4- and 8-week MH model groups were significantly increased, while those of the MH+aspirin groups were significantly decreased. There was no significant change in the IL-10 level or PGI2 level at 4 weeks. At 8 weeks, the PGI2 level was significantly decreased in the MH model group while significantly increased in the MH+aspirin group. The TXA2 levels were significantly increased in the 4- and 8-week MH model groups and those in the 4- and 8-week MH+aspirin groups were significantly lower. Aspirin has an anti-inflammatory effect, can effectively reduce the expression of inflammatory factors, inhibit myocardial apoptosis, and has a certain protective effect against MH.


Assuntos
Aspirina/farmacologia , Cardiotônicos/farmacologia , Miocárdio/patologia , Animais , Apoptose/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Colágenos Fibrilares/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipertrofia , Mediadores da Inflamação/metabolismo , Interleucina-10/sangue , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Tamanho do Órgão/efeitos dos fármacos , Prostaglandinas/sangue , Ratos Wistar , Tromboxano A2/sangue , Fator de Necrose Tumoral alfa/sangue
6.
BMJ Case Rep ; 14(4)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: covidwho-1194192

RESUMO

Emerging evidence suggests that novel COVID-19 is associated with increased prothrombotic state and risk of thromboembolic complications, particularly in severe disease. COVID-19 is known to predispose to both venous and arterial thrombotic disease. We describe a case of a 61-year-old woman with history of type II diabetes, hypertension and hyperlipidaemia who presented with dry cough and acute abdominal pain. She was found to have a significantly elevated D-dimer, prompting imaging that showed thrombi in her right ventricle and aorta. She had rapid clinical deterioration and eventually required tissue plasminogen activator with subsequent durable clinical improvement. This case highlights a rare co-occurrence of venous and arterial thrombi in a patient with severe COVID-19. Further studies are needed to clarify the molecular mechanism of COVID-19 coagulopathy, the utility of D-dimer to predict and stratify risk of thrombosis in COVID-19, and the use of fibrinolytic therapy in patients with COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Trombose , Aorta/patologia , COVID-19/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Trombose/complicações , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico
7.
Med Sci Monit ; 27: e929512, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33866323

RESUMO

BACKGROUND Sepsis is a serious clinical problem that results from the systemic response of the body to infection. Left ventricular (LV) diastolic dysfunction is increasingly appreciated as a contributor to morbidity and mortality in sepsis. Animal models may offer a method of studying diastolic dysfunction while controlling for many potential clinical confounders, such as sepsis duration, premorbid condition, and therapeutic interventions. This study sought to evaluate an endotoxemia (LPS) rodent model of sepsis, with regard to echocardiographic evidence, including tissue Doppler, of LV diastolic dysfunction and histopathology findings. MATERIAL AND METHODS Fourteen male Sprague-Dawley rats were randomly allocated (1: 1) to LPS or saline (control). Mean arterial blood pressure (MAP) was measured through cannulation of the carotid artery. After a 30-min stabilization, baseline assessment with echocardiography and blood collection was performed. Rats were administered 0.9% saline or LPS (10 mg/mL). Follow-up echocardiography and blood collection were performed after 2 h. Hearts were removed post-mortem and pathology studied using histology and immunohistochemistry. RESULTS LPS was associated with hypotension (MAP 81.86±31.67 mmHg; 124.29±20.16; p=0.02) and LV impaired relaxation (myocardial early diastolic velocity [e'] 0.06±0.02 m/s; 0.09±0.02; P=0.008). Histopathology and immunohistochemistry demonstrated evidence of interstitial myocarditis (hydropic changes and inflammation). CONCLUSIONS LPS was associated with both diastolic dysfunction (impaired relaxation) and interstitial myocarditis. These features may offer a link between the structural and functional changes that have previously been described separately in clinical sepsis. This may facilitate further studies focused upon the mechanism and potential benefit treatment of sepsis-associated cardiac dysfunction.


Assuntos
Ventrículos do Coração/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Sepse/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Animais , Diástole , Modelos Animais de Doenças , Ecocardiografia Doppler , Ventrículos do Coração/patologia , Humanos , Imuno-Histoquímica , Masculino , Miocardite/patologia , Ratos , Ratos Sprague-Dawley , Sepse/patologia , Disfunção Ventricular Esquerda/patologia
8.
Biomed Res Int ; 2021: 6653802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860048

RESUMO

Objective: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Epigenoma , Genoma Humano , Genômica , Transcriptoma/genética , Cardiomiopatia Dilatada/sangue , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
9.
Int J Mol Sci ; 22(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804428

RESUMO

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.


Assuntos
Comunicação Celular , Conexina 43/fisiologia , Junções Comunicantes/fisiologia , Ventrículos do Coração/patologia , Células Musculares/fisiologia , Pericárdio/fisiologia , Ramos Subendocárdicos/fisiologia , Animais , Feminino , Masculino , Camundongos , Células Musculares/citologia , Pericárdio/citologia , Ramos Subendocárdicos/citologia
10.
BMJ Case Rep ; 14(4)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875503

RESUMO

Emerging evidence suggests that novel COVID-19 is associated with increased prothrombotic state and risk of thromboembolic complications, particularly in severe disease. COVID-19 is known to predispose to both venous and arterial thrombotic disease. We describe a case of a 61-year-old woman with history of type II diabetes, hypertension and hyperlipidaemia who presented with dry cough and acute abdominal pain. She was found to have a significantly elevated D-dimer, prompting imaging that showed thrombi in her right ventricle and aorta. She had rapid clinical deterioration and eventually required tissue plasminogen activator with subsequent durable clinical improvement. This case highlights a rare co-occurrence of venous and arterial thrombi in a patient with severe COVID-19. Further studies are needed to clarify the molecular mechanism of COVID-19 coagulopathy, the utility of D-dimer to predict and stratify risk of thrombosis in COVID-19, and the use of fibrinolytic therapy in patients with COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Trombose , Aorta/patologia , COVID-19/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Trombose/complicações , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico
11.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809145

RESUMO

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.


Assuntos
Arritmias Cardíacas/sangue , Infarto do Miocárdio/sangue , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Idoso , Animais , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/cirurgia , Feminino , Hemoglobina A Glicada/genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/genética , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Suínos , Resultado do Tratamento , Troponina/sangue
12.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803922

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation and resistance to apoptosis (as seen in cancer cells) of PA smooth muscle cells (PASMCs) is a major pathological hallmark contributing to pulmonary vascular remodeling in PAH, for which current therapies have only limited effects. Emerging evidence points toward a critical role for Enhancer of Zeste Homolog 2 (EZH2) in cancer cell proliferation and survival. However, its role in PAH remains largely unknown. The aim of this study was to determine whether EZH2 represents a new factor critically involved in the abnormal phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell-cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and tricarboxylic acid cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteoma/genética , Hipertensão Arterial Pulmonar/genética , Transcriptoma/genética , Animais , Apoptose/genética , Proliferação de Células/genética , Ciclo do Ácido Cítrico/genética , Epigênese Genética/genética , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/crescimento & desenvolvimento , Artéria Pulmonar/patologia , Ratos
13.
Nutrients ; 13(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652586

RESUMO

Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress. Male c57BL6 mice were randomly divided into an ad libitum (AL) diet or 40% restricted diet (DR preconditioning, DRPC) group for 2 weeks prior to ascending aortic constriction (AAC), and all mice were fed ad libitum after AAC surgery. Two weeks after surgery, pressure overload by AAC increased LV wall thickness in association with LV diastolic dysfunction and promoted myocyte hypertrophy and cardiac fibrosis in the AL+AAC group. Oxidative stress in cardiac tissue and mitochondria also increased in the AL+AAC group in association with increments in cardiac NADPH oxidase-derived and mitochondrial ROS production. LV hypertrophy and associated cardiac dysfunction and oxidative stress were significantly attenuated in the DRPC+AAC group. Moreover, less severe mitochondrial oxidative damage in the DRPC+AAC group was associated with the suppression of mitochondrial permeability transition and cardiac apoptosis. These results indicate that chronic pressure overload-induced cardiac hypertrophy in association with cardiac and mitochondrial oxidative damage were attenuated by preconditioning with short-term DR.


Assuntos
Restrição Calórica/métodos , Insuficiência Cardíaca/prevenção & controle , Hipertrofia Ventricular Esquerda/prevenção & controle , Estresse Oxidativo/fisiologia , Cuidados Pré-Operatórios/métodos , Animais , Aorta/cirurgia , Apoptose , Constrição , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/prevenção & controle
14.
Clin Exp Hypertens ; 43(5): 419-427, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-33715564

RESUMO

Background: The impact of age on the association between central aortic hemodynamics and left ventricular (LV) remodeling has not been well elucidated. We compared the relationship between measurements of central blood pressure (CBP) and LV mass index (LVMI) according to their ages (<50 years versus ≥50 years). Methods: A total of 305 consecutive subjects (64.4 ± 10.9 years, 60.7% males) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were prospectively enrolled. Just before ICA, CBP was measured at the aortic root using a pig-tail catheter, and CBP indices, including aortic systolic blood pressure (aSBP), aortic pulse pressure (aPP), aortic fractional pulse pressure (=aPP/mean aortic pressure), and aortic pulsatility index (=aPP/diastolic aortic pressure), were recorded. All subjects underwent transthoracic echocardiography, and LVMI was measured on the same day of ICA. Results: In simple linear correlation analyses, LVMI was associated with all CBP indices in subjects aged <50 years (n = 29) (P < .05 for each), but not in those aged ≥50 years (n = 276) (P > .05 for each). In the younger age group (≤50 years), multivariable analysis showed that aSBP (ß = 0.457, P= .021) and aPP (ß = 0.610, P= .006) had a significant association with LVMI after adjusting for possible confounding factors. The results remained consistent even when analyzed in a 1:1 propensity score-matched cohort. In conclusion, invasively measured aPP showed the closest association with LVMI in subjects aged <50 years, but not those aged ≥50 years. Conclusion: Aortic pulsatile hemodynamic status appears to have a greater effect on LV remodeling in younger people than in older people.


Assuntos
Envelhecimento/patologia , Pressão Sanguínea/fisiologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Adulto , Fatores Etários , Idoso , Pressão Arterial/fisiologia , Estudos de Coortes , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Hemodinâmica/fisiologia , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pontuação de Propensão
15.
Am J Cardiol ; 149: 47-56, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33757785

RESUMO

COPD often coexists with HFpEF, but its impact on cardiovascular structure and function in HFpEF is incompletely understood. We aimed to compare cardiovascular phenotypes in patients with Chronic Obstructive Pulmonary Disease (COPD), Heart Failure with Preserved Ejection Fraction (HFpEF), or both. We studied 159 subjects with COPD alone (n = 48), HFpEF alone (n = 79) and HFpEF + COPD (n = 32). We used MRI and arterial tonometry to assess cardiac structure and function, thoracic aortic stiffness, and measures of body composition. Relative to participants with COPD only, those with HFpEF with or without COPD exhibited a greater prevalence of female sex and obesity, whereas those with HFpEF + COPD were more often African-American. Compared to the other groups, participants with HFpEF and COPD demonstrated a more concentric LV geometry (LV wall-cavity ratio 1.2, 95%CI: 1.1-1.3; p = 0.003), a greater LV mass (67.4, 95%CI: 60.7-74.2; p = 0.03, and LV extracellular volume (49.4, 95%CI: 40.9-57.9; p = 0.002). Patients with comorbid HFpEF + COPD also exhibited greater thoracic aortic stiffness assessed by pulse-wave velocity (11.3, 95% CI: 8.7-14.0 m/s; p = 0.004) and pulsatile load imposed by the ascending aorta as measured by aortic characteristic impedance (139 dsc; 95%CI=111-166; p = 0.005). Participants with HFpEF, with or without COPD, exhibited greater abdominal and pericardial fat, without difference in thoracic skeletal muscle size. In conclusion, individuals with co-morbid HFpEF and COPD have a greater degree of systemic large artery stiffening, LV remodeling, and LV fibrosis than those with either condition alone.


Assuntos
Composição Corporal , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Obesidade/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Rigidez Vascular/fisiologia , Remodelação Ventricular/fisiologia , Gordura Abdominal , Tecido Adiposo , Afro-Americanos , Idoso , Estudos de Casos e Controles , Comorbidade , Grupo com Ancestrais do Continente Europeu , Feminino , Fibrose , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Tamanho do Órgão , Pericárdio , Fenótipo , Fluxo Pulsátil , Análise de Onda de Pulso , Distribuição por Sexo , Volume Sistólico
16.
J Clin Ultrasound ; 49(5): 520-524, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33719039

RESUMO

Endomyocardial fibrosis (EMF), a restrictive cardiomyopathy characterized by subendocardial fibrosis, is commonly seen in tropical and subtropical regions. EMF involving the left ventricle presents with severe pulmonary hypertension (PH) and is a rare cause of PH in non-tropical areas. Multimodality imaging is important for accurate diagnosis, especially cardiac magnetic resonance imaging which is the cornerstone. Herein, we report the case of a patient who presented with heart failure symptoms and severe PH, and in whom EMF was diagnosed by multimodality imaging.


Assuntos
Fibrose Endomiocárdica/complicações , Ventrículos do Coração/patologia , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Imagem Multimodal , Adulto , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
17.
Nat Commun ; 12(1): 1684, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727534

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.


Assuntos
Proteína Forkhead Box O1/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Metabolismo dos Lipídeos , Contração Miocárdica , Volume Sistólico , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Sequência Conservada , Deleção de Genes , Células HEK293 , Insuficiência Cardíaca/genética , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fenótipo , Estabilidade Proteica , Proteólise , Transcrição Genética , Ubiquitina-Proteína Ligases/metabolismo
18.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33604679

RESUMO

MicroRNAs (miRs) are reported to serve key roles in pulmonary arterial hypertension (PAH). miR­1 has been found in cardiovascular diseases. The present study aimed to determine whether the knockdown of miR­1 could inhibit right ventricle (RV) remodeling and thereby control PAH in model rats. PAH model rats were established by exposing rats to hypoxia, while cardiac fibroblasts (CFs) obtained from PAH model rats were treated with hypoxia to establish an in vitro model, and RV remodeling was evaluated by Masson staining and the levels of collagen I, collagen III, α­smooth muscle actin (α­SMA) and connective tissue growth factor (CTGF) evaluated by western blotting or reverse transcription­quantitative PCR. The results revealed that the expression levels of miR­1 were upregulated in the RV of PAH model rats induced with hypoxia and in the CFs treated with hypoxia. The mean pulmonary arterial pressure, RV systolic pressure, RV/(left ventricle + interventricular septum) and RV/tibia length were increased in PAH rats; however, the increases in all parameters were subsequently reversed by transfection with a miR­1 antagomiR in PAH model rats. The transfection with the miR­1 antagomiR inhibited the development of RV fibrosis and downregulated the mRNA expression levels of collagen I, collagen III, α­SMA and CTGF in the RV tissue of PAH model rats. The upregulation of collagen I, collagen III, α­SMA and CTGF expression levels in hypoxia­treated CFs was also subsequently reversed by miR­1 antagomiR transfection. The expression levels of collagen I, collagen III, α­SMA and CTGF were also upregulated in the CFs obtained from PAH model rats, and these increases were attenuated by miR­1 antagomiR transfection. The expression levels of phosphorylated (p)­PI3K and p­AKT were also upregulated in hypoxia­treated CFs, and these increases were also inhibited by transfection with miR­1 antagomiR. In conclusion, these results indicated that inhibiting miR­1 may attenuate RV hypertrophy and fibrosis in PAH model rats, a mechanism that may involve the PI3K/AKT signaling pathway.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Hipertensão Pulmonar Primária Familiar/terapia , MicroRNAs/genética , Hipertensão Arterial Pulmonar/terapia , Animais , Antagomirs/farmacologia , Modelos Animais de Doenças , Hipertensão Pulmonar Primária Familiar/genética , Hipertensão Pulmonar Primária Familiar/patologia , Regulação da Expressão Gênica/genética , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Humanos , MicroRNAs/antagonistas & inibidores , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Remodelação Ventricular/genética
19.
Magn Reson Imaging ; 78: 127-139, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33571634

RESUMO

Left-ventricular (LV) strain measurements with the Displacement Encoding with Stimulated Echoes (DENSE) MRI sequence provide accurate estimates of cardiotoxicity damage related to breast cancer chemotherapy. This study investigated an automated LV chamber quantification tool via segmentation with a supervised deep convolutional neural network (DCNN) before strain analysis with DENSE images. Segmentation for chamber quantification analysis was conducted with a custom DeepLabV3+ DCNN with ResNet-50 backbone on 42 female breast cancer datasets (22 training-sets, eight validation-sets and 12 independent test-sets). Parameters such as LV end-diastolic diameter (LVEDD) and ejection fraction (LVEF) were quantified, and myocardial strains analyzed with the Radial Point Interpolation Method (RPIM). Myocardial classification was validated against ground-truth with sensitivity-specificity analysis, the metrics of Dice, average perpendicular distance (APD) and Hausdorff-distance. Following segmentation, validation was conducted with the Cronbach's Alpha (C-Alpha) intraclass correlation coefficient between LV chamber quantification results with DENSE and Steady State Free Precession (SSFP) acquisitions and a vendor tool-based method to segment the DENSE data, and similarly for myocardial strain analysis in the chambers. The results of myocardial classification from segmentation of the DENSE data were accuracy = 97%, Dice = 0.89 and APD = 2.4 mm in the test-set. The C-Alpha correlations from comparing chamber quantification results between the segmented DENSE and SSFP data and vendor tool-based method were 0.97 for LVEF (56 ± 7% vs 55 ± 7% vs 55 ± 6%, p = 0.6) and 0.77 for LVEDD (4.6 ± 0.4 cm vs 4.5 ± 0.3 cm vs 4.5 ± 0.3 cm, p = 0.8). The validation metrics against ground-truth and equivalent parameters obtained from the SSFP segmentation and vendor tool-based comparisons show that the DCNN approach is applicable for automated LV chamber quantification and subsequent strain analysis in cardiotoxicity.


Assuntos
Cardiotoxicidade/diagnóstico por imagem , Aprendizado Profundo , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Automação , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/patologia , Feminino , Humanos , Semântica , Sensibilidade e Especificidade
20.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578743

RESUMO

The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3DNGR1-KO mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNFα-induced protein-3 (Tnfaip3) gene, encoding the NF-κB regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3DNGR1-KO mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3DNGR1-KO mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3DNGR1-KO mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 (Bmpr2), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene.


Assuntos
Células Dendríticas/imunologia , Hipertensão Pulmonar Primária Familiar/imunologia , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Células Dendríticas/patologia , Hipertensão Pulmonar Primária Familiar/genética , Hipertensão Pulmonar Primária Familiar/patologia , Deleção de Genes , Ventrículos do Coração/imunologia , Ventrículos do Coração/patologia , Humanos , Imunidade Inata , Camundongos , Mutação , Receptor 4 Toll-Like/imunologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...