Prevention of cardiac hypertrophy in mice by calcineurin inhibition
Prevention of cardiac hypertrophy in mice by calcineurin inhibition
复制标题
DOI：
10.1126/science.281.5383.1690
复制
发表时间：
1998-09-11
期刊：
影响因子：
56.9
通讯作者：
Molkentin, JD
中科院分区：
文献类型：
--
作者：
Sussman, MA;Lim, HW;Molkentin, JD
肥厚型心肌病(HCM)是一种遗传性心脏病，每500人中就有1人患病。钙调神经磷酸酶是一种受钙调节的磷酸酶，在肥厚性心肌病的发病机制中起着重要作用。给予钙调神经磷酸酶抑制剂环孢菌素和FK506可以预防因心脏中原调节蛋白、肌球蛋白轻链-2或胎儿β-原肌球蛋白异常表达而遗传易患肥厚性心肌病的小鼠的疾病。环孢素在压力超负荷肥厚的大鼠模型中也有类似的作用。这些结果表明，钙调神经磷酸酶抑制剂作为治疗某些形式的人类心脏病的潜在疗法值得研究。
Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin Light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.