Effect Of Trihydroxyflavone On Angiotensin Ⅱ - Induced Formation Of Abdominal Aortic

An abdominal aortic aneurysm (AAA) is a permanent, localized dilatation of the abdominal aorta (beginning at the level of the diaphragm and extending to its bifurcation into the left and right common iliac arteries). AAA mainly happens in elder men aged65-85. In western countries, the morbidity of AAA is approximately9%. Due to the lack of typical syndrome, its mortality of AAA caused by aortic rupture is almost90%. Currently, AAA therapies mainly include medical treatment and surgical approaches(open repair and endovascular aneurysm repair). The chief function of medical treatment, which controls the risk factors, is to indirectly attenuate aneurysm development and rupture through regulating blood pressure, serum lipid level and blood coagulation. Therefore, developping new drugs that targeting the mechanism of AAA formation is of great significance to AAA prevention and treatment.The pathogenesis of AAA mainly occurs within vascular media, including oxidative stress, inflammation, extracellular matrix degradation and vascular smooth muscle cell (VSMC) apoptosis. These pathogenic processes always correlate with each other to promote the AAA progression. Thus, developping new drugs that targeting these pathogenic processes may provide new therapeutic targets for AAA therapy.Baicalein (BAI) is the main component of Chinese traditional drug "Huang Qin", which is involved in oxidative stress, inflammation, tumorigenesis and angiogenesis. It has been reported that BAI remarkably retards the myocardium injury after ischemia/reperfusion. But its exact mechanism remains elusive and its role in AAA formation has not been proved, ngiotensin â… (Angâ…¡) is an important member of rennin-angiotensin system (RAS). Apoe-/-mice infused with Angâ…¡ is a typical AAA model, which mimics almost all the pathogenic processes of AAA formation. We suggest that BAI represses AAA formation in Apoe-/-mice infused with Angâ…¡, whose mechanism may be related to oxidative stress, vascular inflammation and ECM degradation.We randomly divided experimental mice into3groups:control, BAI low dose and BAI high dose. Above all we examined the AAA formation after BAI injection intraperitoneally. After Angâ…¡ infusion for4weeks, we found that both the incidence and severity of AAA were repressed. Then we discussed the potential mechanism from3different views:Oxidative stress is the first. DHE staining indicated that BAI markedly decreased the ROS production within aortic wall. The second is vascular inflammation. The infiltration of pro-inflammatory cells after Angâ…¡ infusion in the aorta of BAI-treated mice was attenuated compared with that of control group. The last is ECM degradation. We found both MMP-2and MMP-9activation were inhibited in aortas from BAI-treated mice. In addition, BAI also blocked Angll cascade by downregulating AT1R and inhibiting MAPKs. There was no difference between BAI low dose group and high dose group in all the results aboveConclusions:We first find BAI protects against Angâ…¡-induced AAA formation in vivo by blocking vascular inflammation, MMPs activation and oxidative stress. Our findings may provide new drugs for AAA treatment.