High Fat-High Sucrose diet induced vascular endothelial dysfunction, fibrosis and stiffness involve elevated arginase activity

Prevalence of obesity and hyperglycemia is a global health epidemic. Metabolic syndrome, a cluster of hyperglycemia, hypertension, and obesity, is associated with vascular dysfunctions such as impaired endothelial-dependent vasorelaxation and arterial stiffening. Mechanisms involved in these pathogenesis are not well understood. Elevated arginase activity, implicated in many cardiovascular diseases, has been identified to promote endothelial dysfunction by reducing nitric oxide production. Less of a focus has been given to the other side of arginine metabolism where ornithine, product of arginase, can potentially promote vascular proliferation and collagen formation through elevated proline and polyamines. We hypothesized that elevated arginase activity is involved in vascular dysfunction and fibrosis/stiffening associated with obesity-related diabetes. In our study, we fed wild-type (WT) or endothelial-specific arginase 1 knockout (EC-A1−/−) mice (C57BL/6J) a high fat-high sucrose (HFHS) diet for 6 month...