AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress

Abstract

AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.

Anti‐atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis

“…This includes pulmonary remodelling, inflammation and right ventricular hypertrophy in models of allergic asthma (Rodrigues‐Machado et al , ), as well as its protective effects in stroke (Lee et al , ) or liver cirrhosis (Klein et al , ). Mechanisms of the vasoprotective effects of AVE0991 include inhibition of oxidative stress (Ma et al , ), stimulation of eNOS activation and NO production (Pawlik et al , ). It also exerts effects in the CNS, decreasing sympathetic outflow and renal effects leading to changes in the renal proteome, in trems of antioxidant enzymes, apoptosis regulators, inflammatory factors and metabolic enzymes (Suski et al , ).…”

“…It also exerts effects in the CNS, decreasing sympathetic outflow and renal effects leading to changes in the renal proteome, in trems of antioxidant enzymes, apoptosis regulators, inflammatory factors and metabolic enzymes (Suski et al , ). AVE0991 also inhibits p22phox(Jawien et al , ) and Nox2 and Nox4 NADPH oxidases (Ma et al , ) and thus can change the pro‐ and anti‐oxidant balance, indirectly affecting vascular inflammation (Guzik et al , ).…”

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

“…AVE0991 was found to be 10-fold more potent than ANG (1–7) in competing for [ 125 I]-ANG (1–7) binding to, and 5-fold more potent than ANG (1–7) to induce NO release from bovine aortic endothelial cells [207], suggesting that AVE0991 may act as a nonpeptide agonist for the Mas receptor [208,209]. Subsequent in vivo studies have reported that AVE0991 significantly protected postischemic heart failure in rats [210], prevented diabetes-induced cardiovascular dysfunction [211], inhibited atherogenesis in apoE-knockout mice [212,213], ameliorated inflammation in experimental arthritis [214], and attenuated cardiac hypertrophy [215]. Despite these reported protective effects in different animal models or diseases, no clinical trial for AVE0991 is currently registered since it was developed more than 10 years ago [207].…”

Radical Scavenger Capacity of Jabuticaba Fruit (Myrciaria cauliflora) and Its Biological Effects in Hypertensive Rats

“…In the heart and kidneys, the increase in blood pressure has a direct relationship to damage and hypertrophy, which is characterized by an increase in organ volume and weight [27]. The weight of the heart and kidneys also was measured after six weeks of experiments.…”