Endothelial cell CD36 ablation attenuates obesity-induced endothelial dysfunction

Obesity is a prevalent metabolic condition that is strongly associated with the development of cardiovascular disease. Adipose arteries exhibit robust endothelial dysfunction in diet-induced obese mice. Obesity is also associated with elevated plasma long chain fatty acids (LCFAs), well-established contributors to endothelial dysfunction, which require a receptor to facilitate their uptake. CD36, facilitates LCFA uptake which when in excess contributes to endothelial dysfunction. Our previous work demonstrated that global CD36 ablation restores endothelium-dependent dilations to flow. Therefore, to determine if an upregulation in CD36 expression was driving these differences, we first assessed if obesity alters endothelial CD36 expression using flow cytometry and immunofluorescence imaging. For flow cytometry experiments mesenteric arteries were digested and sorted to identify the endothelial cell population (i.e., CD45-CD31+ cells). En face preparations were stained for VE-cadherin to locate the endothelial cell layer using confocal microscopy. In both experiments, an antibody that detects an extracellular epitope of CD36 was used to detect membrane expression. Obesity did not alter the expression of CD36 in endothelium of mesenteric arteries relative to lean counterpart controls in WT mice. We next aimed to determine if obesity influences the functional capacity of endothelial CD36. First, we measured LCFA uptake in mesenteric arteries from lean and obese WT mice. Arteries were exposed to a fluorescent palmitic acid analogue, BODIPYC-16, and internalized endothelial LCFA uptake was assessed at different time points using confocal microscopy. Arteries from obese mice had elevated endothelial LCFA uptake and lipid accumulation relative to lean controls. To determine if the effects of obesity on LCFA uptake were mediated by endothelial CD36, we repeated the fluorescent LCFA uptake experiments using the Tie2eCreCD36 fl/fl model. First, to determine if endothelial cell CD36 was driving obesity induced endothelial dysfunction, mesenteric arteries were isolated from lean and diet-induced obese Tie2eCreCD36 fl/fl mice. Arteries from Tie2eCreCD36 fl/fl diet induced obese mice exhibited attenuated fatty acid uptake, compared to their lean and obese genotype controls. Next, we measured endothelial function ex vivo via pressure myography. Mesenteric arteries from obese Tie2eCreCD36 fl/fl mice exhibited a restored response to flow induced vasodilation relative to respective controls suggesting a role for endothelial cell CD36 in mediating endothelial dysfunction perhaps through promoting lipid accumulation in obesity. Ongoing work within our lab is aimed at determining the mechanism underlying obesity-induced alterations to endothelial CD36 and how the observed increase in LCFAs may be contributing to reduced endothelial function. Center of Biomedical Research Excellence in Cardiovascular Health (COBRE): 5P20GM113125-08, University of Delaware Research Fund (UDRF) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.