Abstract 428: Shear Stress-Induced Mitochondrial Biogenesis: Implications for Salutary Effects of Aerobic Exercise on Endothelial Homeostasis
Enhancing structural/functional integrity of mitochondria in the vascular endothelium has emerged as a novel therapeutic approach for vascular disease. Aerobic exercise stimulates mitochondrial biogenesis via a shear stress (SS)-dependent mechanism in the vasculature. However, functional consequences of SS-induced mitochondrial remodeling in the vascular endothelium remain largely unknown. The purpose of this study was to examine effects of aerobic exercise on endothelial activation/apoptosis and to elucidate the underlying mechanism. In in vivo study, twenty-one prehypertensive individuals underwent a 6-month supervised aerobic exercise training (65% HRmax, 40 min/day, 3 days/week). In in vitro study, cultured Human Umbilical Vein Endothelial Cells (HUVECs) were exposed to SS using a cone-and-plate shear apparatus. Endothelial cells (ECs) were harvested for protein analysis and cell-culture media were collected to assess endothelial microparticle (EMP) production. Antimycin A, SIRT1 siRNA and PGC-1α siRNA were used for the disruption of mitochondrial functional/structural integrity. Protein expressions were analyzed by western-blotting. EMP productions were measured by flow cytometry. Circulating levels of activated (CD62E+) and apoptotic (CD31+/CD42a-) EMPs were significantly decreased (49±6 to 20±2 and 4.0 to 2.4 events/μL, respectively p<0.01) after 6-month aerobic exercise training in prehypertensives. In ECs, laminar SS attenuated productions of activated EMPs (3.18 to 1.43 events/μL) and apoptotic EMPs (0.24 to 0.07 events/μL), which were accompanied by an increase in mitochondrial content (7.8-fold increase). SIRT1 knockdown using siRNA completely abolished the protective effect of laminar SS. Disruption of mitochondrial integrity by either antimycin A or PGC-1α siRNA provoked the activated- (1.7-fold and 2.4-fold increase, respectively) and apoptotic- statuses (2.1-fold and 1.7-fold increase, respectively) and shear stress normalized these impairments. In conclusion, aerobic exercise attenuates endothelial activation and apoptosis by SS-induced mitochondrial biogenesis. This study expands the understanding of implications of mitochondrial biogenesis in endothelial cell homeostasis.
Author Disclosures: J. Kim: None. B. Kim: None. H. Lee: None. S. Thakkar: None. D.M. Babbitt: None. S. Eguchi: None. M.D. Brown: None. J. Park: None.
- © 2014 by American Heart Association, Inc.