Cardiovascular oxidative stress: recent findings on ACE2 And MAO

Oxidative stress is associated with development and progression of cardiovascular disease. Angiotensin II produces oxidative stress and endothelial dysfunction, and its actions may be attenuated by the activity of angiotensin converting enzyme type 2 (ACE2) which converts angiotensin II to the vasoprotective peptide angiotensin (1-7). Similarly, increased oxidative stress is associated with aortic valve stenosis in humans and mice. In my thesis studies, I explore mechanisms of modulation and generation of oxidative stress in cerebral arteries and heart valves. First, I tested the hypothesis that ACE2 deficiency increases oxidative stress and vasomotor dysfunction in cerebral arteries, and examined the role of ACE2 in vascular aging. Vasomotor function was assessed in the basilar artery ex vivo of adult and old ACE2 deficient (ACE2) and wild type (WT or ACE2) mice. ACE2 was present, but at relatively low levels in cerebral arteries. Systolic blood pressure was similar in adult and old ACE2 and ACE2 mice. Maximal dilatation to acetylcholine was impaired in the basilar artery from adult ACE2 mice compared to adult ACE2. In old mice, maximal vasodilatation to acetylcholine was impaired in ACE2 mice and severely impaired in ACE2 mice. The antioxidant tempol improved responses to acetylcholine in adult and old ACE2 and ACE2 mice. Nitrotyrosine staining in the basilar artery was increased in adult ACE2 mice and in old ACE2 and ACE2 mice relative to adult ACE2, which indicates that oxidative stress was higher in cerebral arteries from ACE2 deficient mice and old mice. Expression of NADPH oxidase subunits Nox2 and p47phox, and of pro-inflammatory molecules Rcan1 and TNFα, was increased in cerebral arteries from old ACE2 and ACE2 mice.