Sirtuin 3 is essential for hypertension‐induced cardiac fibrosis via mediating pericyte transition

Autor: Han Su, Heng Zeng, Jian-Xiong Chen, Bo Liu
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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