Different angiogenesis effect of mini-TyrRS/mini-TrpRS by systemic administration of modified siRNAs in rats with acute myocardial infarction

Abstract

We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates with acute myocardial infarction, by delivering small interfering RNAs (siRNAs) systemically in a liposomal formulation. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini-TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP), and administered by intravenous injection to rats. Rats were divided into four experiment groups: sham operated group (no left anterior descending artery [LAD] occlusion); negative control group (LAD occlusion + saline injection); mock transfection group (LAD occlusion + mock transfected injection); experiment group (LAD occlusion + mini-TyrRS/mini-TrpRS-specific siRNAs injection). Silencing efficiency was assayed by Western blotting. To determine whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with myocardial infarction, we measured the myocardial infarction size by TTC staining, and the capillary density using immunohistochemistry staining, to investigate the expression of factor VIII. The myocardial infarction size and the capillary density of mini-TyrRS-siRNA group were respectively 18.89% and 8.64/0.1 mm(2) 1 month after ligation, while in the mini-TrpRS-siRNA group these values were 7.33% and 17.32/0.1 mm(2), significantly different compared with the mock transfection group (14.19%; 13.56/0.1 mm(2)) and negative control group (14.28%; 13.89/0.1 mm(2)), P < 0.05. There were no significant changes between the mock transfection group and the negative control group, P > 0.05. These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in rat models with acute myocardial infarction.