The effect of Telmisartan on the expression of connexin43 and neointimal hyperplasia in a rabbit iliac artery restenosis model

Abstract

We established a rabbit iliac artery restenosis model to explore the impact of Telmisartan on the expression of Connexin43 (Cx43) and neointimal hyperplasia. Thirty New Zealand white rabbits were randomly divided into three groups: control group (n = 10), restenosis group (n = 10), and Telmisartan group (n = 10). The restenosis model was established by high-cholesterol diet combined with double-balloon injury of iliac arteries. In addition, Telmisartan at 5 mg/(kg day) was administered to the rabbits of Telmisartan group on the second day after the second balloon injury. All rabbits were killed at the end of the experiment followed by institution policy. Before sacrifice, blood samples were obtained to test serum angiotensinII (AngII). Iliac arteries were isolated for morphological analysis and determining the expression of Cx43 by HE staining, immunohistochemical analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western Blotting analysis. Then, the local AngII levels of arteries were measured by radioimmunoassay. As compared with controls, the expression of Cx43 mRNA (0.98 ± 0.08) vs. (1.27 ± 0.17), P < 0.01), and Cx43 protein [(0.75 ± 0.08) vs. (0.90 ± 0.08), P < 0.05] of restenosis group were increased, which were significantly higher than those of Telmisartan group [Cx43 mRNA: (1.27 ± 0.17) vs. (1.00 ± 0.20), P < 0.01; Cx43 protein: (0.90 ± 0.08) vs. (0.82 ± 0.05), P < 0.05]. Furthermore, The intima thickness [(266.12 ± 70.27) vs. (2.85 ± 0.19) μm, P < 0.01] and the local AngII [(115.6 ± 15.7) vs. (90.1 ± 7.7), P < 0.05] of restenosis group were raised when compared with controls. Telmisartan group exhibited thinner intima compared with restenosis group [(68.22 ± 24.37) vs. (266.12 ± 70.27), P < 0.01]. However, the local AngII levels between these two groups were approximate. In addition, the plasma concentration of AngII was not significantly different among three groups. In conclusion, Telmisartan can inhibit the expression of connexin43 and neointimal hyperplasia in iliac artery restenosis model.

Keywords: Angiotensin II; Connexin43; Neointimal hyperplasia; Restenosis; Telmisartan; vascular smooth muscle cells.