Abstract 274: Cd36-mediated Lipid Metabolism Promotes Endothelial Cell Angiogenic Function and Vascular Repair Ina Hindlimb Ischemia Mouse Model

Under physiological conditions, endothelial cells (ECs) play an important role in maintaining vascular integrity by acting as non-thrombogenic and non-inflammatory cells. ECs also mediate vascular repair and angiogenesis, a process by which new blood vessels are formed from pre- existing blood vessels. Hyperglycemia has been shown to alter EC angiogenic potential. However, few studies have investigated the effect of fatty acids (FAs) on EC growth and migration. CD36 is an important FA transporter expressed by ECs. We hypothesize that circulating FAs regulate angiogenic function in a CD36-dependent manner. To test this, we studied EC proliferation and migration of control and CD36 deficient mouse heart and lung ECs. siRNA- and ASO-mediated knockdown of CD36 in ECs treated with oleic acid (OA) did not affect EC proliferation. However, in wound healing experiments, OA significantly increased the migration of ECs, whereas CD36 knockdown prevented the OA-induced increase in wound healing potential. In EC transwell migration experiments, OA stimulation, which increased the recruitment and migration of ECs, was not found after CD36 knockdown. Thus, our in vitro results suggest that loss of CD36 hinders EC angiogenic function. In control mice, 21-day recovery post-hindlimb ischemia increased EC content in muscle, as assessed by measuring CD31 and MMP9 expression, compared to that found at baseline in normal muscle. Mice with EC-specific CD36 deletion also showed increased CD31 and MMP9 expression. However, no further increase was

found in EC-specific CD36 knockout ischemic muscle compared to normal muscle. Thus, our in vivo data suggest that the response to ischemia—increasing EC marker expression—is lost with EC-specific CD36 deficiency.