Sirtuin 3 is essential for hypertension‐induced cardiac fibrosis via mediating pericyte transition
Autor: | Han Su, Heng Zeng, Jian-Xiong Chen, Bo Liu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cardiac function curve medicine.medical_specialty hypertension SIRT3 Cardiac fibrosis Fluorescent Antibody Technique Gene Expression sirtuin 3 pericytes Transforming Growth Factor beta1 Mice 03 medical and health sciences 0302 clinical medicine Fibrosis Internal medicine Ventricular Dysfunction medicine Animals Myofibroblasts Fibroblast Cells Cultured reactive oxygen species Mice Knockout cardiac dysfunction transforming growth factor beta 1 Chemistry Angiotensin II fibrosis Original Articles Cell Biology medicine.disease Immunohistochemistry Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Echocardiography 030220 oncology & carcinogenesis cardiovascular system Molecular Medicine Original Article Pericyte Cardiomyopathies Myofibroblast Biomarkers Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-4934 1582-1838 |
Popis: | Hypertension is the key factor for the development of cardiac fibrosis and diastolic dysfunction. Our previous study showed that knockout of sirtuin 3 (SIRT3) resulted in diastolic dysfunction in mice. In the present study, we explored the role of SIRT3 in angiotensin II (Ang‐II)–induced cardiac fibrosis and pericyte‐myofibroblast transition. NG2 tracing reporter NG2‐DsRed mouse was crossed with wild‐type (WT) mice and SIRT3KO mice. Cardiac function, cardiac fibrosis and reactive oxygen species (ROS) were measured. Mice infused with Ang‐II for 28 days showed a significant reduction of SIRT3 expression in the mouse hearts. Knockout of SIRT3 sensitized Ang‐II‐induced elevation of isovolumic relaxation time (IVRT) and reduction of ejection fraction (EF) and fractional shortening (FS). Ang‐II‐induced cardiac fibrosis, capillary rarefaction and hypertrophy were further enhanced by knockout of SIRT3. NG2 pericyte tracing reporter mice infused with Ang‐II had a significantly increased number of NG2‐DsRed pericyte in the heart. Knockout of SIRT3 further enhanced Ang‐II‐induced increase of pericytes. To examine pericyte‐myofibroblast/fibroblast transition, DsRed pericytes were co‐stained with FSP‐1 and α‐SMA. Ang‐II infusion led to a significant increase in numbers of DsRed+/FSP‐1+ and DsRed+/α‐SMA+ cells, while SIRT3KO further developed pericyte‐myofibroblast/fibroblast transition. In addition, knockout of SIRT3 promoted Ang‐II‐induced NADPH oxidase‐derived ROS formation together with increased expression of transforming growth factor beta 1 (TGF‐β1). We concluded that Ang‐II induced cardiac fibrosis partly by the mechanisms involving SIRT3‐mediated pericyte‐myofibroblast/fibroblast transition and ROS‐TGF‐β1 pathway. |
Databáze: | OpenAIRE |
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