Increased Muscle Mass Restores a Healthy Vascular Endothelial Cell Phenotype in Obesity

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ObjectiveInvestigate the effects of hypermuscularity on expression of genes vital to healthy endothelial function in a model of obesity‐driven cardiovascular disease.Methodsdb/db mice, a well characterized model of human obesity, were crossed with mice lacking myostatin, a myokine that inhibits muscle growth, to generate lean, obese, and hypermuscular obese mice. Using a column separation technique, fresh endothelial cells were isolated from the aortic and mesenteric arteries and mRNA expression of genes vital to endothelial health were assessed by qPCR.ResultsThe current study found that obesity significantly (p<0.05) increases expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase 1 (NOX1) by 15 to 25‐fold in both aortic and mesenteric endothelial cells in comparison to lean controls. Interestingly, expression of galectin‐3 (Gal‐3) in obesity increased significantly by 50‐fold in aortic endothelial cells, but 150‐fold in mesenteric endothelial cells. However, in endothelial cells from hypermuscular obese mice, overexpression of both NOX1 and Gal‐3 was ameliorated in both the aortic and mesenteric endothelium. These data indicate that hypermuscularity beneficially alters Gal‐3 overexpression, thereby decreasing injurious effects of NOX1 overexpression and restoring the endothelium to a favorable balance of eNOS and NOX1.ConclusionHypermuscularity improves endothelial NOS/NOX balance by decreasing levels of galectin‐3, an upstream contributor of NOX1 expression. Inhibition of galectin‐3 may prove to be a viable therapeutic target to ameliorate obesity‐driven cardiovascular disease.