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The nonpeptide AVE0991 is an agonist of the angiotensin-(1–7) (Ang-(1–7)) Mas receptor and is expected to be a putative new drug for treatment of cardiovascular disease. However, the mechanisms involved in the antiproliferative effects of AVE0991 are not fully understood. We saw that the compound attenuated proliferation in an angiotensin II-induced rat vascular smooth muscle cells (VSMC) proliferation model. Moreover, treatment with AVE0991 (10−5 mol/L or 10−7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10−8 to 10−5 mol/L) inhibited Ang II-induced VSMC proliferation. Meanwhile, heme oxygenase-1 (HO-1) expression increased in the AVE0991 + Ang II group (10−5 mol/L or 10−6 mol/L). However, the beneficial effects of AVE0991 were completely abolished when the VSMC were pretreated with A-779 (10−6 mol/L). Furthermore, treatment with the HO-1 inhibitor ZnPPIX attenuated the inhibitory effect of AVE0991 on Ang II-induced p38MAPK phosphorylation. These results suggest that AVE0991 attenuates Ang II-induced VSMC proliferation in a dose-dependent fashion and that this effect is associated with the Mas/HO-1/p38 MAPK signaling pathway.

Background: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes. Methods: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications. Results: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62–0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59–0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54–0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27–0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant. Conclusions: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications. [ABSTRACT FROM AUTHOR]

Objective: To explore illness perception (IP) and its predictors among Chinese patients with myocardial infarction (MI). Methods: The revised Illness Perception Questionnaire (IPQ-R) was used in the present study. A cross-sectional, descriptive design was employed. The study was conducted in four major hospitals in Guangzhou (China) with a sample of 193 MI patients. Pearson''s and Spearman''s correlation, t test, one-way ANOVA, factor analysis and multiple linear regression were used. Results: Among the 12 common symptoms of MI, on average only 3.37 were recognized by the subjects. Among the six factors of the cause dimension, “immune factors” received the highest score, followed by “gene and chance”, “behavioral factors”, “psychological factors”, “environmental factors”, and “physical factors”. Subjects perceived MI as a chronic, cyclic illness with serious consequences that could be controlled through treatment, and believed that they had a negative affective response to MI. Furthermore, the dimensions of patients’ IP were correlated, and illness-related factors and socio-demographic factors acted as predictors of IP. Conclusion: The IP of Chinese patients with MI needs to be improved. Practice implications: Based on our findings, effective interventions can be designed to promote MI patients’ IP to facilitate their coping strategies after an episode of MI. [Copyright &y& Elsevier]

Abstract: Objective: Angiotensin-(1–7) [ANG-(1–7)] has been reported to attenuate neointimal formation after vascular injury and stent implantation in rats, but the mechanism remains mostly unresolved. Interestingly, the levels of circulating transforming growth factor-beta1 (TGF-β1) after myocardial infarction were suppressed by ANG-(1–7), which suggests a possible downstream target for the anti-remodeling action of ANG-(1–7). Our study focused on the effects of ANG-(1–7) on vascular remodeling, including neointimal formation and collagen synthesis, and determining whether or not these effects were dependent upon the TGF-β signaling pathway. Methods: Thirty-two New Zealand white rabbits underwent sham surgery or angioplasty in abdominal aorta. The animals were divided into four groups, which were sham, control, ANG-(1–7), and ANG-(1–7)+A-779. Subsequently, an osmotic minipump was implanted to deliver saline, ANG-(1–7) (576μgkg−1 d−1) or ANG-(1–7)+A-779 (576μgkg−1 d−1) for 4weeks. Results: The ANG-(1–7) group displayed a significant reduction in neointimal thickness (207.51±16.70μm vs. 448.08±15.30μm, P <0.001), neointimal area (0.266±0.009mm2 vs. 0.408±0.002mm2, P <0.001), and restenosis rate (28.13±2.74% vs. 40.13±2.74%, P <0.001) when compared to the control group. ANG-(1–7) also inhibited collagen synthesis by significantly decreasing the mRNA expression of Collagen I and Collagen III (vs. Control group: 0.2190±0.0036 vs. 0.3852±0.0212, P <0.001 and 1.1328±0.0554 vs. 1.7378±0.1164, P <0.001, respectively). Furthermore, the expression of TGF-β1 and phosphor-Smad2 (p-Smad2) were significantly suppressed by ANG-(1–7) (vs. Control group: 1.21±0.07 vs. 1.54±0.08, P <0.001 and 0.31±0.01 vs. 0.43±0.02, P <0.001, respectively), but no effect on p38 phosphorylation was observed. [d-Ala7]-ANG-(1–7) (A-779), showed a tendency to attenuate the anti-remodeling effects of ANG-(1–7). Conclusion: ANG-(1–7) decreases the amount of vascular remodeling, including a reduction in neointimal formation and collagen synthesis, after angioplasty in rabbits. The responsible mechanism may function through the possible down-regulation of TGF-β1 levels and inhibition of the Smad2 pathway. [Copyright &y& Elsevier]