Cortistatin attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the ERK1/2 signaling pathways

Abstract

Abdominal aortic aneurysm (AAA) is a fatal disease that is associated with chronic inflammation in the vessel wall. Cortistatin is implicated in inflammation, vascular smooth muscle cell migration and other cardiovascular pathologies. But, the hypothetical effect of cortistatin on AAA remains uncertain. We investigated the effect of cortistatin administration to angiotensin (Ang) II-induced AAA formation in apolipoprotein E deficient (Apoe−/−) mice. We showed that cortistatin administration significantly suppresses incidence and severity of AAA in Apoe−/− mice. A significant increase in macrophage infiltration, excretion of inflammatory cytokines, activities and expression levels of MMP2 and MMP9, reactive oxygen species levels and cell apoptosis in aneurysmal aortic wall of Apoe−/− mice infused with Ang-II, and these events were significantly alleviated by co-treatment with cortistatin. Mechanistic studies showed that the protective effects of cortistatin were related to the blocking of ERK1/2 signaling pathways, while does not was not actually affect JNK, P38 phosphorylation.In conclusion, cortistatin appears to play an essential role in the formation of AAA and indicate cortistatin may as novel therapeutic option for AAA.