IgE Affects The Senescence Of Aortic Smooth Muscle Through LincRNA-p21 And Promotes Abdominal Aortic Aneurysm

Abdominal aortic aneurysm(AAA)in which the abdominal aortic wall degenerates and expands more than 50%of the normal vascular diameter,is a pathological state influenced by multiple factors.The end point of AAA is aneurysm rupture and bleeding,leading to the sudden death of patients.AAA rupture is the tenth most common causes of death in developed countries.Its mortality rate is as high as 85%with poor prognosis if it ruptures.Since most AAA patients are asymptomatic and no pharmaceutical currently exists to slow aneurysm growth.It is important to further explore the pathogenesis of abdominal aortic aneurysm.Immunoglobulin E(lgE)activates immunity by binding to mast cells and basophils.It is well-known that IgE and its receptor,Fce?I,play a key role in the development of airway inflammation and remodeling in allergic asthma.Recent studies show that IgE also plays an important role in abdominal aortic aneurysm pathogenesis.And our previous study demonstrated that patients with AAAs had significantly higher plasma IgE levels than those without AAAs.However,the mechanism by which IgE promotes AAA remains unclear.In this study we report that in our Asthma complicated with abdominal aortic aneurysm mouse model,asthma-induced high level of IgE aggravated mouse AAA diameter,AAA incidence,vascular wall elastin degradation and both AAA local and systemic inflammatory response.Especially,we found that asthma-induced high level of IgE also aggravated AAA tissue cell senescence and p21 upregulation.But IgE lost these effects on AAA in IgE receptor Fc?RI knock-out mice.In vitro study revealed that IgE induced smooth muscle cell senescence by increase p21 expression via upregulate lincRNA-p213 without altering the expression of p53.To confirm this mechanism on animal,we suppress the expression of lincRNA-p21 in ApoE-/-mice by tail vein injecting si-mlincRNA-p21 lentivirus particles.As we hypothesis,knockdown of mouse lincRNA-p21 can effectively attenuate AAA exacerbated by asthma,and reduce p21 expression in tumor tissue therefore alleviate cell senescence.In conclusion,this study reveals asthma-induced high IgE level could aggravate AAA relying on Fc?R1.Except for inflammation,IgE also actives the expression of p21 through the upregulation of lincRNA-p21 to induce human aortic smooth muscle cell senescence,which contributes to the formation of AAA.These data suggested that lincRNA-p21 might be a potential therapeutic target for AAA aggravated by asthma.