The Biological Function Of MiR-145 In Mechanical Stretch Induced Vascular Smooth Muscle Cells Of Aortic Dissection

Background: Aortic dissection is a severe aortic disease in which a local rupture in the intima,blood enters the middle layer of the aorta,causing the intima to dissect and form a true and false lumen.It has a rapid onset,high mortality,low early diagnosis rate and lack of effective radical drug treatment,the death rate per hour after the onset of the disease increases by 1-2% in untreated patients.surgery is an effective treatment method.In recent years,the clinical manifestations of aortic dissection in our country are diversified,the age of onset is younger,there are many reports of misdiagnosis and losted diagnosis,and the mortality rate is still higher.There are many factors in the pathogenesis of aortic dissection,and the pathogenesis is still unclear.In-depth research on the pathogenesis of aortic dissection can provide a theoretical basis for discovering new ways to treat the disease.More and more studies had shown that abnormal gene expression in aortic dissection patients is the inheritance of the pathogenesis.This study mainly illustrated the expression of miR-145 in aortic dissection tissues and the biological function of miR-145 in mechanical stretch induced vascular smooth muscle cells of aortic dissection.Objective:The differences in the expression of miR-145 in the tissues of normal people and aortic dissection patients were detected to verify the involvement of miR-145 in the occurrence and development of aortic dissection.We investigated the expression of SMAD3 in normal people and aortic dissection patients and to study the effect of SMAD3 on the biological function of vascular smooth muscle cells.Further,we investigated the effects of miR-145 on the proliferation and apoptosis of vascular smooth muscle cells induced by mechanical stretch by interfering with the expression of miR-145.Methods: The aortic vessels of 5 patients with aortic dissection and 5 patients with heart transplantation donors were taken,and the middle of aortic wall was isolated,RT-q PCR method was used to detect the difference in the expression level of miR-145 in the tissues of normal people and aortic dissection patients.Vascular smooth muscle cells were extracted and cultured from the middle of aortic wall of aortic dissection patients.The cultured vascular smooth muscle cells were transfected with miR-145 mimic and RT-q PCR was used to detect the transfection of vascular smooth muscle cells.the expression of SMAD3 in the middle of aortic wall of normal people and aortic dissection patients was detected by immunohistochemistry and Western Blot.The cultured vascular smooth muscle cells were divided into four groups: static culture group,static + stretch group,miR-145 mimic group,miR-145mimic+ stretch group,The programmed cell death protein(PDCD4),SMAD3 and proliferating cell nuclear antigen(PCNA)were detected by Western Blot.Results:miR-145 was expressed in tissues of normal people and aortic dissection patients,and the expression in aortic dissection tissues was significantly decreased compared with normal people.RT-q PCR analysis showed that miR-145 was significantly up-regulated in transfected vascular smooth muscle cells(P<0.05).The expression of SMAD3 in vessels tissues of aortic dissection was increased compared with normal people;the expressions of PCNA,PDCD4 and SMAD3 in mechanical stretch induced vascular smooth muscle cells were significantly increased compared with the static group(P<0.05).After miR-145 was overexpressed,the expression of PCNA in vascular smooth muscle cells was decreased than that in the static group(P<0.05),while the expression of PDCD4 and SMAD3 was not significantly difference(P>0.05).After a certain amount of mechanical stretch intervention was applied to vascular smooth muscle cells of overexpressing miR-145,there was no significant difference in the expression of PCNA,PDCD4 and SMAD3 compared with the static group(P>0.05).The expression of PCNA,PDCD4 and SMAD3 in vascular smooth muscle cells of overexpressing miR-145 was significantly decreased compared with the static group under mechanical stretch induction,and the difference was statistically significant(P<0.05).Conclusion: Hsa-miR-145 may affect the proliferation and apoptosis of vascular smooth muscle cells by regulating the expression of SMAD3,while mechanical stretch promoted the occurrence and development of aortic dissection by down-regulating hsa-miR-145.Mechanical stretch induced vascular smooth muscle cells proliferation and apoptosis,while miR-145 maintained vascular smooth muscle cells homeostasis under mechanical stretch induction.