Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1

Abstract

Vascular dysfunctions in diet-induced obesity are prevented by deletion of arginase 1 in vascular endothelial cells or arginase inhibition. These findings indicate that upregulation of arginase 1 expression/activity in vascular endothelial cells has an integral role in diet-induced cardiovascular dysfunction and metabolic syndrome.

Arginase inhibition improves endothelial function in patients with type 2 diabetes mellitus despite intensive glucose‐lowering therapy

“…The major differences between healthy subjects and patients with T2DM in the current study, beyond indices of glucose, are BMI and waist/hip ratio. Previous studies have pointed out that arginase plays a central role in vascular dysfunction in obesity, which suggest that obesity could confound our results . However, El Assar et al .…”

“… have shown that high glucose induces up‐regulation of arginase 1 in bovine coronary endothelial cells via a mechanism involving NADPH oxidase‐derived ROS and up‐regulation of Rho kinase, which in turn reduces NO bioavailability. Moreover, it has been shown that ED induced by ex vivo exposure to high glucose/palmitate was completely reversed by acute administration of an arginase inhibitor . Collectively, these data suggest an intriguing interaction between glucose and arginase in T2DM in the regulation of endothelial function.…”

“…Moreover, arginase inhibition also improves microvascular endothelial function in patients with T2DM . It has also been shown that arginase activity is increased by glucose and ROS in endothelial cells in vitro . These findings suggest that hyperglycaemia triggers activation of arginase which contributes to ED in T2DM.…”

Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

“…Diabetes is an independent risk factor for vascular complications (such as atherosclerosis of the coronary artery and stroke) and a main cause of the prevalence and mortality of cardiovascular diseases . Vascular dysfunction results from a chronic hyperglycaemic state, which leads to increased oxidative stress, vascular fibrosis and thickening, resulting in arteriosclerosis . In diabetic patients, arteriosclerosis is an important and dangerous complication.…”

Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity

“…Factors involved in the pathogenesis of diabetic retinopathy include inflammation, oxidative stress, and reduced endothelial nitric oxide (NO) production [3][4][5][6]. Studies have indicated that obesity and diabetes substantially affect the retina and its interactive vascular, neuronal, glial, and immune cells [5,7].We, and others, previously reported the crucial role of arginase in the development of diabetes-induced pathologies and dysfunctions [3,[8][9][10]. Arginase, a key enzyme in the urea cycle, can reciprocally regulate NO production by competing with nitric oxide synthase (NOS) for their shared substrate, L-arginine [11,12].…”