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

第一项研究是为了研究Ras Pathway的作用，它与中性元主义联系在一起，是因为它是在受约束的Myocyte hypertroy的机制中。Stretch increased RNA/DNA ratio， protein/DNA ratio and rates of protein synthesis。Stretch increased protein kinase C （PKC）活性， mitogen-activated protein （MAP）激酶活性和c-fos mRNA expression。一种选择性PKC抑制剂，钙蛋白C在PKC活性中预防了拉伸诱导的酶，但一种3-羟基-3-甲基谷氨酰辅酶A （HMG-CoA）还原酶抑制剂，左旋抑素没有。Lovastin很好，如钙蛋白C部分但明显地抑制了MAP激酶活性、c-fos mRNA表达和蛋白质合成中的受拉伸诱导的增加。与洛夫斯塔丁和钙蛋白两者结合使用的预处理C完全抑制了这些参数的增加。Lovastatin就像钙蛋白C预防性心肌梗死诱导性心肌梗死。以下是关于机械拉伸M的结果。 ... More 如果激活了Ras通路，那么它将神经元代谢与文化新生大鼠心脏细胞联系起来，第二项研究将用于确定HMG-CoA还原酶抑制剂、洛夫他汀、辛伐他汀和普伐他汀抑制血管紧张素II诱导的超营养生长。Angiotensin II significantly increased protein/DNA ratio， RNA/DNA ratio， ratias of protein synthesis and MAP kinase activity。脂溶性HMG-CoA还原酶抑制剂、左旋司汀和辛伐他汀部分地抑制了血管紧张素II诱导的增加，但一种水溶性HMG-CoA还原酶抑制剂，左旋司汀没有。Mevalonate过度引起了洛夫他汀和辛伐他汀对血管紧张素II的抑制作用-在这些参数中引起的增加。Calphostin C特别和显著地预防的血管紧张素II-在这些参数和治疗中受到了抑制，对所有的洛伐他汀和Calphostin C都完全被抑制。Angiotensin II increased p21イイD1 rasイD1 activity and membrane association， and lovastatin inhibited them。这些研究证明了脂质-可溶性HMG-CoA还原酶抑制剂、洛夫他汀、可预防血管紧张素II诱导的心脏病超负荷，至少在部分中，通过p21-D1 ras-D1 MAP激酶途径，将其与中性代谢联系起来。Less（低）

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