Correction to: AVE0991, a nonpeptide angiotensin-(1-7) mimic, inhibits angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.

The corrected Figure 7 image is presented in this paper.

AVE0991, a nonpeptide angiotensin-(1-7) mimic, inhibits angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.

AVE0991, a nonpeptide angiotensin-(1-7) mimic, has similar protective effects for cardiovascular system to Ang-(1-7). In this article, we aimed to explore the effects of AVE0991 and Ang-(1-7) on abdominal aortic aneurysm (AAA) induced by Ang II in apolipoprotein E knockout mice. The mice AAA model was established by Ang II infusion, and then mice received different treatment with saline, Ang II (1.44 mg/kg/day), different dose AVE0991 (0.58 or 1.16 µmol/kg/day), or Ang-(1-7) (400 ng/kg/min). The incidence of AAA was 76%, 48%, 28%, and 24% in the vehicle, the low-dose AVE0991, high-dose AVE0991, and the Ang-(1-7) group, respectively. In comparison with control group, AVE0991 and Ang-(1-7) treatment significantly increased smooth muscle cells and decreased macrophage accumulation, the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α), and the expression and activity of metalloproteinases 2 and 9 in mice AAA model or in human smooth muscle cells (hVSMCs). The therapeutic effects may be contributed to reduction of oxidative stress and downregulation of P38 and ERK1/2 signal pathways via Mas receptor activation, whereas the positive impacts were reversed by co-administration with the Mas antagonist A779 (400 ng/kg/min) and AVE0991 in Ang II-infused mice or in hVSMCs. Therefore, AVE0991 and Ang-(1-7) might be novel and promising interventions in the prevention and treatment of AAA. KEY MESSAGES: • AVE0991 dose-dependently inhibited Ang II-induced AAA formation in Apoe-/- mice. • Ang-(1-7) played the same protective role as high-dose AVE0991. • Inhibition of Mas receptor with A779 could reverse the protective effect of AVE0991. • The therapeutic effects may be contributed to reduction of oxidative stress and downregulation of P38 and ERK1/2 signal pathways via Mas receptor activation.

Pro-Renin Receptor Overexpression Promotes Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apolipoprotein E-Knockout Mice.

The pro-renin receptor (PRR) is an important novel component of the renin-angiotensin (Ang) system that has multiple functions, which are not yet completely understood. In this study, we aimed to explore the effect of PRR on the formation of Ang II-induced abdominal aortic aneurysm (AAA) in apolipoprotein E-knockout mice. We used Ang II (1.44 mg/kg/day) infusion to induce AAA followed by a treatment of saline, telmisartan, no treatment, Ad-EGFP, Ad-PRR, or Ad-PRR plus telmisartan. The incidence of AAA was 35%, 60%, 65%, 90%, and 55% in the Telmisartan, Vehicle, Ad-EGFP, Ad-PRR, and Ad-PRR+Telmisartan groups, respectively. Compared with the Vehicle and Ad-EGFP groups, PRR overexpression markedly increased macrophage infiltration; levels of proinflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α); the expression and activity of MMP2 and MMP9; NOX2 and NOX4 protein and mRNA expression; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity; extracellular-signal-regulated kinase (ERK) and P38MAPK expression; but decreased smooth muscle cells content in AAA. However, telmisartan reversed the adverse effects of PRR. In addition, ERK inhibitor PD98059 eliminated the acceleration of Ang II-induced AAA formation by PRR, and coadministration of telmisartan and PD98059 further abolished the adverse effects of PRR on Ang II-induced AAA formation. Thus, PRR plays an important role in the pathological development of AAA via both Ang II-dependent and Ang II-independent activation of ERK pathways. These results suggest that inhibition of PRR activation may be a promising approach to the treatment of AAA.

Angiotensin-converting enzyme 2 overexpression protects against doxorubicin-induced cardiomyopathy by multiple mechanisms in rats.

Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups. The rats of Ad-EGFP and Ad-ACE2 groups received intramyocardial injection of Ad-EGFP and Ad-ACE2, respectively. The rats of Cilazapril group received cilazapril (10 mg/kg/day) via intragastric intubation. Apoptosis, inflammation, oxidative stress, cardiac function, the extent of myocardial fibrosis, and levels of ACE2, ACE, angiotensin II (AngII), and angiotensin (1-7) were evaluated. Four weeks after ACE2 gene transfer, the Ad-ACE2 group showed not only reduced apoptosis, inflammatory response, oxidative stress, left ventricular (LV) volume, extent of myocardial fibrosis and mortality of rats, but also increased LV ejection fraction and ACE2 expression level compared with the Mock and Ad-EGFP groups. ACE2 overexpression was superior to cilazapril in improving doxorubicin-induced cardiomyopathy. The putative mechanisms may involve activation of the AMPK and PI3K-AKT pathways, inhibition of the ERK pathway, decrease of TGF-ß1 expression, and interactions of shifting RAS components, such as decreased myocardium AngII levels, increased myocardium Ang (1-7) levels, and reduced ACE expression. Thus, ACE2 may be a novel therapeutic approach to prevent and treat doxorubicin-induced cardiomyopathy.