Fan Zhang1, Naixuan Cheng1, Jie Du1,2,3, Haibo Zhang4, Congcong Zhang5,6,7. 1. Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 2. Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China. 3. Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China. 4. Beijing Anzhen Hospital, Capital Medical University, Beijing, China. zhanghb2318@163.com. 5. Beijing Anzhen Hospital, Capital Medical University, Beijing, China. zcc_anzhen@163.com. 6. Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China. zcc_anzhen@163.com. 7. Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China. zcc_anzhen@163.com.
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.
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: Tomasz Mazurek; LiFeng Zhang; Andrew Zalewski; John D Mannion; James T Diehl; Hwyda Arafat; Lea Sarov-Blat; Shawn O'Brien; Elizabeth A Keiper; Anthony G Johnson; Jack Martin; Barry J Goldstein; Yi Shi Journal: Circulation Date: 2003-10-27 Impact factor: 29.690
Authors: Hoda Y Abdallah; Ranya Hassan; Ahmed Fareed; Mai Abdelgawad; Sally Abdallah Mostafa; Eman Abdel-Moemen Mohammed Journal: BMC Cardiovasc Disord Date: 2022-06-24 Impact factor: 2.174