Buttrick P, Malhotra A, Factor S, Greenen D, Leinwand L, Scheuer J
Department of Medicine, Montefiore Medical Center, Bronx, N.Y. 10467.
Circ Res. 1991 Mar;68(3):645-52. doi: 10.1161/01.res.68.3.645.
The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.
老年心脏适应诸如高血压等叠加压力负荷的机制尚未得到描述。因此，我们研究了24月龄大鼠心脏在肾血管性高血压状态下的生化和分子遗传学适应性变化。与4月龄大鼠相比，衰老伴随着左心室质量增加68%，而心脏重量与体重之比无变化，钙激活肌球蛋白ATP酶活性降低33%，并且肌球蛋白重链（MHC）同工型分布从以V1为主转变为以V3为主。α-MHC mRNA减少46%，β-MHC mRNA相应增加。当叠加高血压时，心室质量进一步增加75%，心脏重量与体重之比增加63%，肌球蛋白ATP酶减少19%。肌球蛋白同工酶分布进一步向V3转变，α-MHC与β-MHC mRNA的比值降低。此外，高血压状态下心脏肌浆网钙激活ATP酶的mRNA水平显著降低（超过50%）。这些数据表明，老年心肌能够以类似于年轻动物的分子遗传学和蛋白质合成模式的肥大反应来应对叠加的压力负荷。
