The NADPH oxidase Nox4 has anti-atherosclerotic functions

Abstract

The H2O2-producing NADPH oxidase Nox4 is an endogenous anti-atherosclerotic enzyme. Nox4 inhibitors, currently under clinical evaluation, should be carefully monitored for cardiovascular side-effects.

Reactive Oxygen Species Generation and Atherosclerosis

“…25 On the other hand, Nox4 in Apoe −/− mice had a protective effect both in mice with spontaneous atherosclerosis development or after partial carotid artery ligation. 26 Nox4 deletion led to the decrease in H 2 O 2 in mouse aortas, associated with the increase in superoxide levels. Microarray analysis of gene expression in WT or Nox4-deficient animals showed increased proinflammatory signaling in aortas from the Nox4-deficient mice.…”

“…23 Nox4-derived mitochondrial ROS were detrimental in older mice with atherosclerosis, 24 and dominant negative mutant form of Nox4 decreased atherosclerosis formation. 25 On the other hand, Nox4 knockout aggravated atherosclerosis, 26 especially in diabetic mice. 27 High levels of oxidative stress can be counteracted by complex antioxidant cell systems that are crucial for the maintenance of redox balance.…”

Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling

“…While this manuscript was under revision, a paper by Schürmann et al 57 was published suggesting a vasculoprotective effect by Nox4. [1][2][3] .…”

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…30,40 Nox4 −/− leads to increased vascular inflammation, vascular hypertrophy, and endothelial dysfunction, which translates into greater susceptibility to the development of atherosclerosis. 30,41 Nox4 downregulation is also critically linked with the development of VSMC senescent phenotype characterized by lower proliferation and proinflammatory cytokines and matrix metalloproteinase (MMP) secretion. 42 We are now beginning to understand the mechanisms of this protective effect.…”