p47phox is required for atherosclerotic lesion progression in ApoE–/– mice

Atherosclerosis: humoral and cellular factors of inflammation

“…Recently, Wassmann et al [67] demonstrated a marked reduction of atherosclerotic lesions if genetic disruption of the AT1A receptor inhibits vascular oxidative stress and endothelial dysfunction in apoE −/− /AT1A −/− double knockout mice. This study supported the hypothesis that the reduction of oxidative stress, e.g., by antioxidants or by genetics, is associated with an improvement of endothelial function and decreased atherosclerotic lesion formation [3].…”

Oxidative stress and atherosclerosis

“…Inhibition of NADPH activation by a gp91 chimeric peptide blocks O 2 -generation by inhibition of NADPH activation following balloon-induced vascular injury [50••]. These findings are consistent with another study showing reduced atherosclerotic lesion formation in mice lacking the p47phox subunit of NADPH oxidase [17].…”

“…Animal studies have shown increased expression of subunits of the NADPH oxidase and enhanced O 2 -generation in response to vascular injury [16•]. Furthermore, animals with targeted deletion of the regulatory p47phox subunit on an apolipoprotein (ApoE) -/-background exhibit reduced atherosclerotic lesion formation compared with ApoE -/-animals [17].…”

Nitric oxide and oxidative stress in vascular disease

“…A confirmation of the role of NADPH oxidase-derived ROS in hypertension and atherosclerosis came from studies with genetic disruption of subunits of the enzyme. Knockout of the p47phox subunit reduced blood pressure responses to angiotensin II and diminished atherogenesis in apolipoprotein E (apoE) −/− mice [6,65]. Similarly, Nox1-deficient mice show smaller blood pressure increases to angiotensin II [83], whereas mice overexpressing Nox1 in smooth muscle showed greater blood pressure responses to angiotensin II and increased O 2 − · production [21].…”