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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 or10−7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10−8to10−5 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 or10−6 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.

Objectives To evaluated the safety and efficacy of individualised anti-thrombotic therapy in elderly patients with ST-elevated myocardial infarction underwent primary PCI based on age groups. Methods Study population Between Jan. 2007 and Dec. 2008, patients with ST-elevated myocardial infarction eligible for primary PCI was assigned into 3 groups based on their ages: non-elderly group (CON, ≤65), elderly 1(ELD1, 65 75). These patients received individualised anti-thrombotic therapy based on their age group. Non-elderly patients received 300mg aspirin and 600mg clopidogrel loading dose at the emergency department and 10 μg/kg tirofiban loading dose were given intravenous or intra-coronary prior to intervention and followed by 0.15 μg/kg·min infusion for 36 h. Elderly patients received 300 mg aspirin and 300 mg clopidogrel loading dose at the emergency department and tirofiban was given based on the thrombus burden in the culprit vessel. Clinical and angiographic parameters bleeding complications, syntax score, TIMI and CTFC coronary flow, TMP myocardial perfusion grade, in-hospital and long-term MACE, including cardiogenic death, non-fatal re-infarction, target vessel revascularization, re-hospitalisation. Results Between Jan. 2007 and Dec. 2008, 124 patients with ST-elevated myocardial infarction eligible for primary PCI were enrolled. There were 48 patients in control group, 46 patients in ELD1 group, and 30 patients in ELD2 group. Patients in ELD1 group and ELD2 group had more co-morbidity factors. The complexity of coronary lesions was similar in three groups, the SYNTAX score in three groups were 17.7±7.3, 17.0±7.7 and 16.8±6.1 (p=0.829)). The immediate angiographic outcome was also similar in three groups. The CTFC of infarction-related artery in three group were 31.4±14.1, 33.3±16.9 and 32.5±13.8 (p=0.279)). TMP-3 perfusion were achieved in 79.2%, 71.2% and 80% patients in 3 groups. TIMI-3 flow were achieved in 87.5%, 86.9% and 86.6% patients in 3 groups. There were no fatal bleeding and TIMI major bleeding in both groups. There was a trend of increased TIMI minor bleeding risk in ELD2 group patients. Conclusion Our single-center and single-operator experience indicate that individualised aggressive anti-thrombotic therapy for elderly patients with ST-elevated myocardial infarction underwent primary PCI could improve myocardial perfusion and coronary flow. Individualised aggressive anti-thrombotic therapy for elderly patients with ST-elevated myocardial infarction underwent primary PCI did not increase the bleeding risk.