Deficiency of peroxisome proliferator-activated receptor α attenuates apoptosis and promotes migration of vascular smooth muscle cells

Abstract

Peroxisome proliferator-activated receptor (PPAR) α is widely expressed in the vasculature and has pleiotropic and lipid-lowering independent effects, but its role in the growth and function of vascular smooth muscle cells (VSMCs) during vascular pathophysiology is still unclear. Herein, VSMC-specific PPARα-deficient mice ( Ppara ΔSMC ) were generated by Cre-LoxP site-specific recombinase technology and VSMCs were isolated from mice aorta. PPARα deficiency attenuated VSMC apoptosis induced by angiotensin (Ang) II and hydrogen peroxide, and increased the migration of Ang II-challenged cells.

Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach

“…[49,50] PPAR𝛼 is ubiquitously expressed, including in endothelial cells and VSMCs in the vasculature. [51,52] We may therefore speculate that the changes in PBMC gene expression observed in our study is reflecting gene expression changes in the liver and the vasculature.…”

Peroxisome Proliferator-Activated Receptor α Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Angiotensin II-Induced ROS Production

“…It is worth exploring the mechanistic link between PPARα and the mitochondrial function in VSMCs on a more detailed molecular basis. In addition to its role in attenuating the mitochondrial ROS production and maintaining the mitochondrial membrane potential, our previous work has also demonstrated that a PPARα deficiency can attenuate VSMC apoptosis induced by Ang II and hydrogen peroxide, and increase the migration of Ang II-challenged VSMCs [ 22 ], thus indicating a profound and complex role for PPARα in maintaining VSMCs homeostasis. Although we detected a PPARα reduction in VSMCs accelerated Ang II-induced mitochondrial oxidative stress, we did not further explore the PPARα target genes in VSMCs to establish a direct mechanistic link between mitochondrial dysfunction and hypertensive vascular remodeling.…”

“…Ppara fl/fl mice on a C57BL/6J background were generated as previously described [ 21 ]. Ppara fl/fl mice were crossed with SM22α-Cre to produce VSMC-specific Ppara -deficient mice ( Ppara ΔSMC ) [ 22 ]. Two-month-old Ppara ΔSMC and Ppara fl/fl male mice were infused with saline or Ang II at 490 ng/kg per minute with micro-osmotic pumps (Alzet, Model 1004, Cupertino, CA, USA) for 28 days as described [ 23 ].…”