• The Effects of Caveolin-1 on Mitochondrial Dynamics

      Eguchi, Satoru; Rizzo, Victor; Ramirez, Servio H.; Scalia, Rosario (Temple University. Libraries, 2018)
      Cardiovascular disease (CVD) is the leading global cause of death. Coronary Artery Disease (CAD) is a grouping of the most common cardiovascular diseases and is the current leading cause of death in developed countries. Treatments for CAD include pharmaceuticals as well as surgical interventions such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting. However, these treatments do not completely remove the risk of adverse outcomes. Endothelial dysfunction is the underlying cause of CAD and is initiated by the chronic inflammation of the vasculature due to increased oxidative stress and production of reactive oxygen species (ROS). Previous studies have shown that the deletion of caveolin, a signaling molecules abundant within endothelial cells, can enhance inflammatory responses and lead to increased oxidative stress and ROS production. Mitochondrial ROS created from dysfunctional mitochondrial dynamics has also been shown to contribute to the inflammation of the endothelium. We hypothesize that due to the link between caveolin and endothelial dysfunction, and the link between mitochondria and endothelial dysfunction, caveolin has an important function in mitochondrial dynamics and that the loss of caveolin increases the mitochondrial fission via a Drp1-dependent pathway. Our data shows that adenoviral silencing of caveolin-1 in rat aortic endothelial cells increases Drp1 expression but does not significantly alter mitochondrial morphology. Overexpression of caveolin-1 via an adenoviral construct in these cells produces a decrease in Drp1 expression without altering mitochondrial morphology. This data provides insight into the pathophysiology of CAD and could provide us with new therapeutic targets in the future.