[Role of CaN-NFATc3 pathway in abdominal aorta restenosis following ballon dilatation in rats].

OBJECTIVE: To investegate the role of calcineurin (CaN) and its downstream nuclear factor of activated T-cells (NFATc3) in abdominal aorta restenosis following balloon dilatation in rats. METHODS: SD rats were randomly divided into sham-operated group, balloon group and cyclosporine A (CsA) group. The rats in the latter two groups were subjected to abdominal aorta injury with balloon dilatation, and those in CsA group were treated with CsA at the daily dose of 12.5 mg/kg from 3 days before the surgery to the end of the experiment. Thirty days afer the injury, histological analysis of the arterial wall was carried out with HE staining and immunohistochemistry. The expressions of CaN and NFATc3 in the abdominal aortas were detected with rea1-time PCR, and serum concentration of MCP-1 was determined using enzyme-linked immunosorbent assay. RESULTS: Intimal hyperplasia with irregular thickness of the neointima was observed in the aorta of rats with ballon injury. In rats with CsA treatment, the area of the intimal layers and the ratio of the intimal to the medial layers were obviously lower than those in the balloon injury group (P<0.05). Compared to those in the sham-operated group, the expressions of calcineurin protein and mRNA and NFATc3 mRNA in the arterial wall and serum level of MCP-1 increased significantly in the ballon injury group (P<0.05). CsA treatment significantly suppressed aorta restenosis and the alterations of CaN, NFATc3 and serum MCP-1 induced by ballon dilatation (P<0.05). CONCLUSIONS: CaN-NFATc3 signal transduction pathway mediates restenosis of rat abdominal aorta following ballon dilatation, and CsA can attenuate the restenosis by suppressing this pathway.

Alterations in cardiac structure and function in a modified rat model of myocardial hypertrophy.

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.

MicroRNA-26 was decreased in rat cardiac hypertrophy model and may be a promising therapeutic target.

MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3ß (GSK3ß) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3ß expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3ß gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3ß signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.