A Study Of MicroRNA-21-3p As A Novel Potential Biomarker For Diagnosing Aortic Aneurysm/Aortic Dissection And Related Mechanisms

Objectives: This study was designed to validate the different expression of micro RNA-21-3p in aortic aneurysm(AA)/aortic dissection(AD)patients and normal controls to discuss its value to the diagnosis of AA/AD and to explore the possible mechanisms.Methods: On the basis of previous research results,we collected plasma samples from AA/AD patients and normal controls from Department of Cardiovascular Surgery,the First Affiliated Hospital of Soochow University to verify the expression of mi RNA-21-3p in Quantitative Real-time polymerase chain reaction(q PCR).Then,the model of murine thoracic aortic aneurysm(TAA)was constructed.And the expression of mi RNA-21-3p in mice plasma was measured by q PCR at four different stages during the modeling period.The possible mechanisms of mi RNA-21-3p on the formation and progression of AA/AD was explored through cell culture,cell transfection,immunofluorescence staining,q PCR and other experiments.Results:Using q PCR,we demonstrated that the expression of mi RNA-21-3p in the plasma of AA/AD patients was significantly upregulated(3.85�1.64 VS 1.04�0.59,p<0.05).In vivo experiment,ultrasound imaging showed a significant increase in expansion of the thoracic aortic diameter after 4 weeks for Ang?-infused mice compared with control mice(p<0.05).And we found out that the expression of mi RNA-21-3p in Ang?-infused mice plasma increased gradually,and the expression level increased remarkably after 4 weeks(p<0.05).Then we performed in vitro experiments using primary human aortic smooth muscle cells(HASMCs)and human aortic endothelial cells(HAECs)and confirmed that mi RNA-21-3p expression is up-regulated in HASMCs of AA/AD patients(p<0.05).We modulated mi RNA-21-3p using a mi RNA-mimic to enhance expression in HASMCs,and confirmed that the expression of contractile phenotype marker ?-SMA was down-regulated markedly in mi RNA-21-3p mimic group compared with mi RNA-21-3p NC group.On the contrary,the expression of synthetic phenotype marker SMemb was up-regulated significantly in mi RNA-21-3p mimic group(p<0.05).Conclusions: The expression of mi RNA-21-3p in plasma of AA/AD patients was significantly increased and similar result was found in murine TAA model which suggests that mi RNA-21-3p might be a potential diagnostic biomarker of AA/AD.Murine TAA model can be successfully constructed by intraperitoneal injection of angiotensin ? and high-fat diet feeding Apo E-/-mice for 28 days.mi RNA-21-3p is highly possibly involved in AA/AD development by regulating the phenotype transformation of vascular smooth muscle cell(VSMC).