Effects of losartan on expression of connexins at the early stage of atherosclerosis in rabbits

Abstract

Aim: to investigate effects of Losartan on expression of connexin 40 and 43 (C×40 and C×43), in arteries at the early stage of atherosclerosis in a rabbit model. Methods: A total of 28 male New Zealand white rabbits were divided into following groups: control group, high fat diet group, and Losartan group (10 mg/kg/day). Losartan was administrated in food for two weeks. Iliac arteries were obtained for immunohistochemistry, transmission electron mi-croscopy, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Transmission electron microscopy revealed abundant gap junctions between neointimal smooth muscle cells (SMCs), which were markedly reduced by treatment. RT-PCR and Western blot assay showed that the mRNA and protein expression of C×40 and C×43 were elevated in the neointimal area at the early stage of atherosclerosis. The mRNA and protein expression of C×43 were significantly down-regulated by losartan treatment but those of Cx40 were not markedly changed. Conclusion: Cx40 and C×43 in the neointimal SMCs were up-regulated at the early stage of atherosclerosis. Losartan (an angioten- sin-converting enzyme inhibitor) could reduce neointima proliferation and down-regulate the elevated protein expression of C×43, suggesting the rennin-angiotensin system (RAS) plays an important role in the remodeling of gap junction between ventricular myocytes under pathological conditions. © Ivyspring International Publisher.