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Increased Muscle Mass Restores a Healthy Vascular Endothelial Cell Phenotype in Obesity
Author(s) -
Padgett Caleb A.,
Butcher Joshua T.,
Corley Zachary L.,
Mintz James D.,
Fulton David J.,
Stepp David W.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00075
Subject(s) - enos , medicine , endocrinology , endothelial dysfunction , endothelium , nox1 , mesenteric arteries , vascular endothelial growth factor b , endothelial stem cell , nadph oxidase , nitric oxide , biology , vascular endothelial growth factor a , nitric oxide synthase , artery , vascular endothelial growth factor , biochemistry , in vitro , oxidative stress , vegf receptors
Objective Investigate the effects of hypermuscularity on expression of genes vital to healthy endothelial function in a model of obesity‐driven cardiovascular disease. Methods db/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. Results The 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. Conclusion Hypermuscularity 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.