PGC1a regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia

PGC1a regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia microscopy revealed that intimal injury disrupted the balance of vascular energy metabolism and impaired the mitochondrial ultrastructure in vivo. The human carotid plaque and femoral artery plaque samples also exhibited alterations in mitochondrial morphology. Vascular smooth muscle cells (VSMCs) are the main components of neointimal hyperplasia and are subjected to cyclic stretch resulting from pulsatile pressure. In this study, we found that the application of cyclic stretch in vitro increased VSMC mitochondrial mass and function. In addition, peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1a) played an important role in regulating VSMC mitochondrial function in response to physiological stretch via the phosphorylation of Smad3. Increasing the activation of PGC1a by ZLN005 treatment effectively inhibited VSMC hyperproliferation after intimal injury in vivo. These results suggested that the regulation of PGC1a by p-Smad3 in response to physiological cyclic stretch may effectively alleviate neointimal hyperplasia by promoting mitochondrial function. PGC1a may be a potential therapeutic target for the prevention and treatment of neointimal hyperplasia. Overall design: RNA-seq profiling of left carotid artery (injury group) and right carotid artery (control group) in 4-week carotid intimal injury model rats