MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis.

Abstract

BACKGROUND:

Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered.

METHODS:

The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H2O2 and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX.

RESULTS:

250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition.

CONCLUSIONS:

Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS.

• Authors: Fan Zhang, Naixuan Cheng, Jie Du, Haibo Zhang, Congcong Zhang
• Journal: BMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 21 Issue 1 Pg. 172 (04 12 2021) ISSN: 1471-2261 [Electronic] England
• PMID: 33845782 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Lipoproteins, LDL
• MIRN200 microRNA, human
• MicroRNAs
• Repressor Proteins
• oxidized low density lipoprotein
• Hydrogen Peroxide
• HDAC4 protein, human
• Histone Deacetylases

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Atherosclerosis (enzymology, genetics, pathology)
• Cells, Cultured
• Coronary Artery Disease (enzymology, genetics, pathology)
• Histone Deacetylases (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, enzymology, pathology)
• Humans
• Hydrogen Peroxide (toxicity)
• Lipoproteins, LDL (toxicity)
• MicroRNAs (genetics, metabolism)
• Oxidative Stress
• Repressor Proteins (genetics, metabolism)
• Signal Transduction