The Role Of Ginkgo Biloba Extract On Angiotensin ?-induced Abdominal Aortic Aneurysm

Objective:Abdominal aortic aneurysms(AAAs)are a chronic vascular disease characterized by pathological luminal dilation.Aortic rupture is the fatal consequence of AAAs.Ginkgo biloba extracts(GBE),a natural herb extract widely used as drugs,food supplements,and cosmetics,has been reported to suppress development of calcium chloride-induced AAAs in mice.Calcium chloride-induced AAAs do not rupture,while angiotensin ?(Ang?)-induced AAAs in mice have high rate of aortic rupture,implicating potentially different mechanisms from calcium chloride-induced AAAs.This study aimed to determine the role of ginkgo biloba extract on angiotensin?-induced abdominal aortic aneurysm.Methods:To determine effects of GBE on Angll-induced AAAs,in the study 1,male apoE-/-mice were administered either vehicle or GBE(100mg/kg/day)through drinking water and infused with Ang? for 28 days.During the experiment and the end,the survival rate,incidence of AAAs,aortic rupture rate and arterial wall pathological changes were observed,the blood pressure,the concentration of cholesterol and inflammatory factors were measured.To design the study 2 according to the result of study 1,and to interpret the potential effective components of GBE on Angll-induced AAAs.We administered both individual and combined active ingredients(flavonoids 40mg/kg/day,ginkgolides 10mg/kg/day)through drinking water in male apoE-/-mice with Ang? infusion for 28 days.During the experiment and the end,the survival rate,incidence of AAAs,aortic rupture rate and arterial wall pathological changes were observed,the blood pressure,the concentration of cholesterol and inflammatory factors were measured.To determine the effects of GBE in mice with established AAAs,in the study 3,male apoE-/-mice were firstly infused with Angll for 28 days to develop AAAs,and then administered either GBE(100mg/kg/day)or vehicle in mice with established AAAs,which were continuously infused with Angll for another 56 days.During the experiment and the end,the survival rate,abdominal aorta dilation,aortic rupture rate and arterial wall pathological changes were observed,the blood pressure,the concentration of cholesterol and inflammatory factors were measured.Results:GBE,but not the two major active components separately or synergistically,prevented aortic rupture,but not aortic dilation or incidence of AAAs.GBE also did not attenuate either aortic rupture or progressive aortic dilation in mice with established AAAs.GBE attenuated elastin breakdown in Ang?-induced mice.Furthermore,GBE did not alter serum total cholesterol concentrations or serum concentrations of proinflammatory cytokines and enzymes,including monocyte chemoattractant protein 1(MCP-1),interleukin 6(IL-6),matrix metalloproteinase 2 and 9(MMP-2,MMP-9).Angll induced a significant increase of systolic blood pressure that was not influenced by administration of GBE.GBE did not reduce the atherosclerotic lesion areas,either.Conclusion:GBE prevents aortic rupture in Angll-infused hypercholesterolemic mice,but only in the early phase of the disease development.This effect is not dependent on its single active pharmaceutical ingredient.GBE attenuates elastin breakdown in Ang?-induced mice.but it does not significantly affect the concentration of serum cholesterol,inflammatory factors(MCP-1,IL-6)and metalloenzymes(MMP-2,MMP-9).