Role of NADH/NADPH Oxidase–Derived H ₂ O ₂ in Angiotensin II–Induced Vascular Hypertrophy

Abstract

Abstract-Recent evidence suggests that oxidative mechanisms may be involved in vascular smooth muscle cell (VSMC) hypertrophy. We previously showed that angiotensin II (Ang II) increases superoxide production by activating an NADH/NADPH oxidase, which contributes to hypertrophy. Key Words: vascular smooth muscle Ⅲ angiotensin II Ⅲ NADH Ⅲ NADPH oxidase Ⅲ hydrogen peroxide Ⅲ superoxide dismutase Ⅲ catalase Ⅲ hypertrophy H ypertension, atherosclerosis, and mechanical injury share many common pathologic effects on the vessel wall, including vascular smooth muscle proliferation, monocyte/macrophage infiltration, dysfunction of regenerated endothelium, and increased deposition of connective tissue.

Endothelial nitric oxide synthase negatively regulates hydrogen peroxide-stimulated AMP-activated protein kinase in endothelial cells

“…Basal intracellular levels of H 2 O 2 , typically in the range of 25-75 M (5), are involved in normal processes of endothelial cell function (6). However, under pathological conditions, excessive ROS production has detrimental consequences in the vascular wall (7).…”

Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation

“…MAPK family members are key signaling molecules for many stimuli including regulation molecules and environmental factors, and ROS have been implicated in activation of ERK1/2 and p38 MAP kinase in VSMC [22]. MAPKs are activated by growth factors and other signaling molecules, and are critical in signaling pathways mediating cellular proliferation and migration [23].…”

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

“…All major cell types of the vascular wall (endothelium, smooth muscle and fibroblasts) contain the enzyme NADPH oxidase, which is responsible for the production of superoxide anion, 83 which is activated in response to Ang II 84 and leads to both hypertension 85 and smoothmuscle cell hypertrophy. 86 Experimental models of atherosclerosis have also demonstrated activation of the local RAS and vascular NADH/NADPH oxidase activity. 87 The ACEis represent a new antioxidant strategy that targets oxidative stress at its source.…”