Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling.

Autor:	Zhong X; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Li Z; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Xu Q; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Peng H; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Su Y; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Le K; Sickle Cell Branch, National heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA., Shu Z; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Liao Y; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Ma Z; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Pan X; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China., Xu S; Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China., Zhou S; School of Chinese Materia Medica, GuangDong Pharmaceutical University.; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, GuangZhou, China.
Jazyk:	angličtina
Zdroj:	Journal of hypertension [J Hypertens] 2023 May 01; Vol. 41 (5), pp. 775-793. Date of Electronic Publication: 2023 Mar 01.
DOI:	10.1097/HJH.0000000000003399
Abstrakt:	Objectives: Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme in the fatty acid oxidation process, is not only involved in ATP synthesis but also regulates the production of mitochondrial reactive oxygen species (ROS) and nitric oxide synthesis. The purpose of this study was to investigate the possible role of SCAD in hypertension-associated vascular remodelling. Methods: In-vivo experiments were performed on spontaneously hypertensive rats (SHRs, ages of 4 weeks to 20 months) and SCAD knockout mice. The aorta sections of hypertensive patients were used for measurement of SCAD expression. In-vitro experiments with t-butylhydroperoxide (tBHP), SCAD siRNA, adenovirus-SCAD (MOI 90) or shear stress (4, 15 dynes/cm 2 ) were performed using human umbilical vein endothelial cells (HUVECs). Results: Compared with age-matched Wistar rats, aortic SCAD expression decreased gradually in SHRs with age. In addition, aerobic exercise training for 8 weeks could significantly increase SCAD expression and enzyme activity in the aortas of SHRs while decreasing vascular remodelling in SHRs. SCAD knockout mice also exhibited aggravated vascular remodelling and cardiovascular dysfunction. Likewise, SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and the aortas of hypertensive patients. SCAD siRNA caused HUVEC apoptosis in vitro , whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Furthermore, SCAD expression was decreased in HUVECs exposed to low shear stress (4 dynes/cm 2 ) and increased in HUVECs exposed to 15 dynes/cm 2 compared with those under static conditions. Conclusion: SCAD is a negative regulator of vascular remodelling and may represent a novel therapeutic target for vascular remodelling. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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