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TGF-β1 and TIMP1 double directional rAAV targeted by UTMD in atherosclerotic vulnerable plaque
Yijin Su1, Changsong Xu1, Kunyu Li1
1Department of Ultrasound, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, P.R. China.
Abstract:
In the present study, we determined whether ultrasound-targeted microbubble destruction (UTMD) combined with dual targeting of transforming growth factor (TGF)-β1 and tissue inhibitors of metalloproteinase (TIMP) 1 recombinant adeno-associated virus (rAAV) can stabilize atherosclerotic vulnerable plaques. First, we used rabbit model to detect the TGF-β1/TIMP1 virus therapy result. H&E staining was used to evaluate the tissues. The protein levels of TGF-β1 and TIMP1 were detected in rabbit models. The THP-1 cells were induced into macrophages, and transfected with TGF-β1 and TIMP1 rAAV under optimized UTMD. The expression of TGF-β1 and TIMP1 was measured by RT-PCR and western blotting. We found that the apoptotic rates were induced when compared to the control group. The rAAV virus group showed a significant decrease in the p-ERT and p-AKT expression. These data support the hypothesis that TGF-β1 and TIMP1 are crucial in the regulation of atherosclerotic plaques.