Affiliation:
1. Department of Cardiovascular Surgery, Peking University Shenzhen
Hospital, Shenzhen City 518036, Guangdong Province, P.R. China
Abstract
Abstract
Objective Diabetic cardiomyopathy (DCM) constitutes a primary cause of
mortality in diabetic patients. Histone deacetylase (HDAC) inhibition can
alleviate diabetes-associated myocardial injury. This study investigated the
mechanism of HDAC1 on myocardial fibrosis (MF) in DCM.
Methods A murine model of DCM was established by a high-fat diet and
streptozotocin injection. The bodyweight, blood glucose, serum insulin, and
cardiac function of mice were analyzed. Lentivirus-packaged sh-HDAC1 was
injected into DCM mice and high glucose (HG)-induced cardiac fibroblasts (CFs).
The pathological structure of the myocardium and the level of myocardial
fibrosis were observed by histological staining. HDAC1 expression in mouse
myocardial tissues and CFs was determined. Collagen I, collagen III,
alpha-smooth muscle actin (α-SMA), and vimentin levels in CFs were
detected, and CF proliferation was tested. HDAC activity and histone acetylation
levels in tissues and cells were measured. Bone morphogenetic protein-7 (BMP-7)
expression in myocardial tissues and CFs was determined. Functional rescue
experiments were conducted to confirm the effects of histone acetylation and
BMP-7 on myocardial fibrosis.
Results DCM mice showed decreased bodyweight, elevated blood glucose and
serum insulin, and cardiac dysfunction. Elevated HDAC1 and reduced BMP-7
expressions were detected in DCM mice and HG-induced CFs. HDAC1 repressed BMP-7
transcription through deacetylation. HDAC1 silencing alleviated MF, reduced CF
proliferation and decreased collagen I, -III, α-SMA, and vimentin
levels. However, reducing histone acetylation level or BMP-7 downregulation
reversed the effects of HDAC1 silencing on CF fibrosis.
Conclusion HDAC1 repressed BMP-7 transcription by enhancing histone
deacetylation, thereby promoting MF and aggravating DCM.
Funder
Diagnosis and treatment of cardiovascular diseases based on glycolysis
3D printing and rapid prototyping
technology in the treatment of Complex abdominal aortic
aneurysm
Subject
Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
2 articles.
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