权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Lovastatin prevents stretch- or angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells

洛伐他汀可预防培养的新生大鼠心脏细胞中拉伸或血管紧张素 II 诱导的心脏肥大

基本信息

批准号：
10670622
负责人：
HANEDA Takashi
金额：
$ 1.66万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670622/
关键词：
heart cell cardiac hypertrophy stretch angiotensin II HMG-CoA reductase inhibitor Protein kinase C Ras protein Mevalonate

项目摘要

The first study was undertaken to investigate the role of the Ras pathway, which is linked to mevalonate metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Stretch increased RNA/DNA ratio, protein/DNA ratio and rates of protein synthesis . Stretch increased protein kinase C (PKC) activity, mitogen-activated protein (MAP) kinase activity and c-fos mRNA expression. A selective PKC inhibitor, calphostin C prevented the stretch-induced increase in PKC activity, but a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, lovastatin did not. Lovastatin as well as calphostin C partially but significantly inhibited the stretch-induced increases in MAP kinase activity, c-fos mRNA expression and protein synthesis. Pretreatment with both lovastatin and calphostin C completely inhibited the increases in these parameters caused by stretch. Lovastatin as well as calphostin C prevents stretch-induced cardiac hypertrophy. These results suggest that mechanical stretch m … More ay activate the Ras pathway, which is linked to mevalonate metabolism, in cultured neonatal rat heart cells.The second study was undertaken to determine whether HMG-CoA reductase inhibitors, lovastatin, simvastatin and pravastatin inhibit the angiotensin II-induced hypertrophic growth. Angiotensin II significantly increased protein/DNA ratio, RNA/DNA ratio, ratias of protein synthesis and MAP kinase activity. Lipid-soluble HMG-CoA reductase inhibitors, lovastatin and simvastatin partially-and significantly inhibited the angiotensin II-induced increases in these parameters, but a water-soluble HMG-CoA reductase inhibitor, pravastatin did not. Mevalonate overcame the inhibitory effects of lovastatin and simvastatin on angiotensin II-induced increases in these parameters. Calphostin C partically and significantly prevented angiotensin II-induced increases in these parameters, and treatment with both lovastatin and calphostin C inhibited completely. Angiotensin II increased p21ィイD1rasィエD1 activity and membrane association, and lovastatin inhibited them. These studies demonstrate that a lipid-soluble HMG-CoA reductase inhibitor, lovastatin, may prevent angiotensin II-induced cardiac hypertrophy, at least in part, through p21ィイD1rasィエD1 MAP kinase pathway, which is linked to mevalonate metabolism. Less

第一项研究是调查Ras途径的作用，这是与甲羟戊酸代谢，在牵张诱导的心肌细胞肥大的机制。拉伸增加RNA/DNA比率、蛋白质/DNA比率和蛋白质合成速率。牵张增加蛋白激酶C（PKC）活性，丝裂原活化蛋白（MAP）激酶活性和c-fos mRNA表达。选择性PKC抑制剂calphostin C阻止了牵张诱导的PKC活性增加，但3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂洛伐他汀没有。洛伐他汀以及calphostin C部分但显着抑制牵张诱导的MAP激酶活性，c-fos mRNA表达和蛋白质合成的增加。预处理与洛伐他汀和calphostin C完全抑制这些参数的增加所造成的拉伸。洛伐他汀和钙磷蛋白C预防牵张性心肌肥大这些结果表明，机械拉伸 ...更多信息 HMG-CoA还原酶抑制剂洛伐他汀、辛伐他汀和普伐他汀对血管紧张素II诱导的心肌肥大生长有抑制作用。血管紧张素Ⅱ可显著增加蛋白质/DNA比值、RNA/DNA比值、蛋白质合成比值和MAP激酶活性。脂溶性HMG-CoA还原酶抑制剂，洛伐他汀和辛伐他汀部分和显着抑制血管紧张素II诱导的这些参数的增加，但水溶性HMG-CoA还原酶抑制剂，普伐他汀没有。甲羟戊酸克服了洛伐他汀和辛伐他汀对血管紧张素II诱导的这些参数增加的抑制作用。Calphostin C部分和显着防止血管紧张素II诱导的这些参数的增加，洛伐他汀和calphostin C治疗完全抑制。血管紧张素II增加p21 β D1 ras β D1活性和膜结合，而洛伐他汀抑制它们。这些研究表明，脂溶性HMG-CoA还原酶抑制剂，洛伐他汀，可以防止血管紧张素II诱导的心肌肥大，至少部分，通过p21 β D1 ras β D1 MAP激酶途径，这是连接到甲羟戊酸代谢。少