Galectin-3 Mediates Vascular Dysfunction in Obesity by Regulating NADPH Oxidase 1

作者：Caleb A. Padgett, Robert Karoly Batori, Andrew C. Speese, Cody L. Rosewater, Weston B. Bush, Cassandra C. Derella, Stephen B. Haigh, Hunter G. Sellers, Zachary L. Corley, Madison A. West, JAMES D. MINTZ, Brittany B. Ange, Ryan Alan Harris, Michael W. Brands, David J. Fulton, David W. Stepp · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2023 · DOI：10.1161/atvbaha.123.319476 · 被引用次数：24 · 研究领域：Galectins and Cancer Biology、Glycosylation and Glycoproteins Research、Atherosclerosis and Cardiovascular Diseases

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease, but underlying mechanisms remain elusive. Metabolic dysfunction, especially hyperglycemia, is thought to be a major contributor, but how glucose impacts vascular function is unclear. GAL3 (galectin-3) is a sugar-binding lectin upregulated by hyperglycemia, but its role as a causative mechanism of cardiovascular disease remains poorly understood. Therefore, the objective of this study was to determine the role of GAL3 in regulating microvascular endothelial vasodilation in obesity. METHODS: mice to generate lean, lean GAL3 knockout, obese, and obese GAL3 knockout genotypes. Endothelial cell-specific GAL3 knockout mice with novel AAV-induced obesity recapitulated whole-body knockout studies to confirm cell specificity. RESULTS: Deletion of GAL3 did not alter body mass, adiposity, or plasma indices of glycemia and lipidemia, but levels of plasma reactive oxygen species as assessed by plasma thiobarbituric acid reactive substances were normalized in obese GAL3 knockout mice. Obese mice exhibited profound endothelial dysfunction and hypertension, both of which were rescued by GAL3 deletion. Isolated microvascular endothelial cells from obese mice had increased expression of NOX1 (nicotinamide adenine dinucleotide phosphate oxidase 1), which we have previously shown to contribute to increased oxidative stress and endothelial dysfunction, which was normalized in microvascular endothelium from mice lacki...