Pathologically Elevated-Cyclic Stretch Suppressed Vascular Smooth Muscle Cell Mitochondrial Biogenesis by Down-regulating PGC1α Expression
10.16156/j.1004-7220.2023.01.23
- VernacularTitle:周期性高张应变通过下调 PGC1α 表达抑制血管平滑肌细胞线粒体生物发生
- Author:
Shoumin ZHANG
1
;
Zhiyin LI
1
;
Wenhao TIAN
1
;
Yuting TAO
1
;
Yingxin QI
1
;
Yue HAN
1
Author Information
1. Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology,Shanghai Jiao Tong University
- Publication Type:Journal Article
- Keywords:
cyclic stretch;
vascular smooth muscle cells ( VSMCs );
mitochondrial biogenesis;
PGC1α;
mitochondrial DNA (mtDNA) copy number;
citrate synthase
- From:
Journal of Medical Biomechanics
2023;38(1):E156-E163
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of pathologically elevated-cyclic stretch induced by hypertension on mitochondrial biogenesis of vascular smooth muscle cells (VSMCs), and the role of PGC1α in this process. Methods The Flexcell-5000T stretch loading system in vitro was applied to VSMCs with a frequency of 1. 25 Hz and an amplitude of 5% or 15% to simulate the mechanical environment under normal physiological or hypertensive pathological conditions respectively. Western blotting and qPCR were used to detect the expression of PGC1α, citrate synthase and mitochondrial DNA (mtDNA) copy number in VSMCs under normal physiological or hypertensive pathological conditions. VSMCs were treated with PGC1α specific activator ZLN005 to promote PGC1α expression or specific interfering fragment siRNA to inhibit PGC1α expression in order to detect the effect on citrate synthase and mtDNA copy number. Results Compared with 5% physiological cyclic stretch, 15% pathologically elevated-cyclic stretch significantly suppressed the expression of PGC1α, citrate synthase and mtDNA copy number in VSMCs. Compared with control group, the protein expression of PGC1α was significantly decreased and increased respectively. When VSMCs transfected with PGC1α siRNA or incubated PGC1α activator ZLN005, the expression of citrate synthase and mtDNA copy number were also significantly down regulated and up-regulated in VSMCs accordingly. Under physiological cyclic stretch conditions, the protein level of PGC1α was significantly down-regulated by PGC1α siRNA, which also significantly down-regulated citrate synthase expression and mtDNA copy number. The protein expression of PGC1α was significantly up-regulated by ZLN005, which also enhanced the expression of citrate synthase and mtDNA copy number. Conclusions The pathological cyclic stretch induced by hypertension significantly down-regulated the expression of citrate synthase and mtDNA copy number via suppressing the expression of PGC1α, resulting in mitochondrial dysfunction of VSMCs. PGC1α may be a potential therapeutic target molecule to alleviate the progression of hypertension.
