官洪山
中国医学科学院阜外医院 心血管内科
INTRODUCTION:Studies have revealed that excessive endoplasmic reticulum (ER) stress leads to apoptosis. Although cardiomyocytes apoptosis contributes to the transition from left ventricular hypertrophy (LVH) to heart failure, it is unknown whether ER stress participates in the pathologic process. The authors first induced coarctation of the abdominal aorta in rats to induce LVH and then investigated the effect of telmisartan on the resulting ER stress.METHODS:Male Sprague-Dawley rats were randomly divided into 3 groups: sham operation, abdominal aortic coarctation (AAC) and AAC + telmisartan. Telmisartan (5 mg · kg · d) or vehicle was infused into the stomach 1 week after the operation. ER stress signaling pathway molecules and apoptosis were studied in pressure-overloaded hearts 9 weeks after AAC.RESULTS:Telmisartan significantly reduced LVH and interstitial fibrosis and improved left ventricular function compared with AAC alone. Cardiac markers of ER stress such as GRP78, C/EBP homologous protein, caspase-12 and phospho c-Jun NH2-terminal kinase were significantly increased in rats with AAC, and telmisartan significantly blunted these changes. Rats that received both telmisartan and AAC had less apoptosis due to ER stress.CONCLUSIONS:Increased ER stress might be responsible for enhanced cardiomyocyte apoptosis after aortic coarctation. Telmisartan may reduce ER stress and thereby attenuate both apoptosis and cardiac hypertrophy.
The American journal of the medical sciences 2011
The proliferation of cardiac fibroblasts (CFs) and excessive extracellular matrix protein accumulation are the basic pathological processes of myocardial fibrosis. Visfatin is a novel adipokine involved in the regulation of inflammatory cytokines, however, the effects of visfatin on proliferation and collagen synthesis of CFs are unclear. The aim of this study was to determine whether visfatin has any effect on the proliferation and collagen synthesis in rat CFs. Incorporation of [ (3)H]-thymidine and [ (3)H]-proline were used for evaluating DNA and collagen synthesis. Flow cytometry techniques were adopted to analyze cell cycle. Enzyme-linked immunosorbent assay was used for measuring collagen type I and III production. RT-PCR and Western blot analysis were used for determining procollagen I and III mRNA expression and protein production. The inhibitors used for pathway determination were: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK)1/2)], and JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin significantly increased DNA and collagen synthesis in a dose- and time-dependent manner. Cell cycle analysis showed that visfatin increased S-stage percentage and proliferation index in a dose- and time-dependent manner. It was also found that visfatin upregulated collagen I and III production, procollagen I and III mRNA expression and protein production. These effects were diminished by SB203580, wortmannin, and PD98059, but not by JNK inhibitor II. These results suggest that visfatin promote CFs proliferation and collagen synthesis via p38MAPK, PI3K, and ERK 1/2 pathways rather than JNK pathways, which also indicate that visfatin might play a role in myocardial fibrosis.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2010
