Role of transglutaminase 2 and Mer receptor tyrosine kinase gene silencing in mouse atherosclerotic plaque losing stability

Objective To evaluate the role of adenovirus vector plasmid targeting both transglutaminase 2 (TG2) and Mer receptor tyrosine kinase (Mertk) in mouse atherosclerotic plaque losing stability.Methods Mouse atherosclerosis (AS) model was established.Thirty mice were divided randomly into pAdTrack/TG2/Mertk group (n =10),pAdTrack/TG2 group (n =10),and pAdTrack/TG2 group (n =10).One side of common iliac artery of each group was transfected locally with corresponding pAdTrack/TG2/Mertk,pAdTrack/TG2 or pAdTrack/TG2.Other side of common iliac artery was transfected locally with pAdTrac/GFP as control group.After 8 weeks,the protein expression of TG2 and Mertk was detected by using Western blotting.Eccentric index (EI) and remodeling index (RI) were calculated by micro-ultrasound measurement,and vulnerable index was calculated.Lipid,collagen,macrophage and smooth muscle cell positive area of AS plaque in each group were examined by using immunohistochemistry.Resuits Compared with pAdTrack/Mertk group and control group,the expression level of TG2 in the AS plaque of pAdTrack/TG2/Mertk group and pAdTrack/TG2 group was decreased obviously (P ＜ 0.01),but there was no significant difference between later two groups.Compared with pAd/TG2 group and control group,the expression level of Mertk in the AS plaque of pAdTrack/TG2/Mertk group and pAdTrack/Mertk group was decreased obviously (P ＜ 0.01),but there was no significant difference between later two groups.Compared with other 3 groups,EI and RI in pAdTrack/TG2/Mertk group was increased obviously (P ＜ 0.05),vulnerable index increased obviously (P ＜ 0.01),lipid increased obviously (P ＜ 0.01),collagen decreased obviously (P ＜ 0.05),and macrophage increased obviously (P ＜ 0.05),but smooth muscle cells showed no significant difference among groups (P ＞ 0.05).Conclusion The adenovirus vector plasmid targeting both TG2 and Mertk plays an important role in mouse atherosclerotic plaque losing stability. Key words: Transglutaminase 2 ;  Mer receptor tyrosine kinase;  Adenovirus;  RNA interference ;  Atherosclerosis plaque