You Position: Home > Paper

Cardiac hypertrophy induced by prostaglandin F2α may be mediated by calcineurin signal transduction pathway in rats

( views:187, downloads:12 )
Author:
No author available
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
6
DOI:
10.3321/j.issn:0371-0874.2005.06.012
Key Word:
前列腺素F2α;心肌肥厚;钙调神经磷酸酶;野百合碱;prostaglandin F2α;cardiac hypertrophy;calcineurin;monocrotaline

Abstract: In this paper, we studied the relationship between the prostaglandin F2α (PGF2α)-induced cardiac hypertrophy and calcineurin (CaN) signal transduction pathway in vivo and in vitro. Male Sprague-Dawley rats were given a single i.p. injection with monocrotaline (MCT) (60 mg/kg) and then given orally with celecoxib (20 mg/kg) or vehicle once a day for 14 d before (from d 1 to d 14) or after (from d 15 to d 28) right ventricular hypertrophy (RVH) was formed. Body weight (BW), right ventricular weight (RV), left ventricular with septum weight (LV), as well as lung weight were determined. RVH index (RVHI=RV/LV), RV/BW, and lung weight/BW were calculated and histological changes were observed with transmission electron microscope. PGF2α level, atrial natriuretic peptide (ANP) and CAN mRNA expressions, expression of CAN and its downstream effectors, NFAT3 and GATA4 protein were assayed by EIA kit, RT-PCR,and Western blotting, respectively. The cardiomyocyte hypertrophy in primary culture induced by PGF2α (0.1 μmol/L) was evaluated by measuring the cell diameter, protein content, and ANP mRNA as well as CaN mRNA expressions. It was found that 14 d or 28 d after MCT was given, the RVHI, RV/BW, and lung weight/BW were significantly increased by 47%, 53% and 118%, and by 64%, 94% and 156%, respectively; at the same time PGF2α levels in RV tissue were increased by 44% and by 51% with increasing RVHI, and elevated expressions of ANP and CaN mRNA, as well as CaN, NFAT3 and GATA4 proteins in a positive correlation manner. Furthermore, some histological injuries were found in RV tissue. Celecoxib, a cyclooxygenase inhibitor, obviously blunted the elevation of RVHI, RV/BW,and lung weight/BW no matter it was given before or after RVH. In vitro experiments showed that 0.1 μmol/L PGF2α significantly increased the cardiomyocyte diameter and protein content, and promoted ANP and CAN mRNA expressions, which was blocked by cyclosporin A, a CaN inhibitor. Our results indicate that PGF2α may be involved in cardiac hypertrophy induced by MCT in rats through CaN signal transduction pathway.

WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn