PROGRESSIVE CHANGES IN MRNA OF RAT CARDIAC HEAVY CHAIN GENES WITH AGING

慢性动脉压引起心肌细胞增大 幼年啮齿动物和血压正常的成年高龄鼠的超负荷 啮齿动物。衰老和压力超负荷心脏的心肌 显示出几乎相同的心脏改变的模式 兴奋-收缩机制，其中包括减少收缩 速度，肌球蛋白ATPase活性的降低，显著增加 V_1(β-肌球蛋白重链，MHC)的表达和 V1(αMHC)亚型。在年轻的高血压成人的心脏 啮齿动物，MHC亚型的这种变化，至少部分是由于 β和αMHC基因的转录。本研究是进行的 确定显著的MHC移位是否随着年龄的增长而发生 成年期和衰老也与MHC基因的变化有关 表情。编码α和βMHC的mRNA水平由 Northern分析和斑点杂交(池RNA上的寡核苷酸探针 从6个不同年龄段的动物的心脏中提纯。基因的信使核糖核酸 从1个月到24个月，贝塔MHC增加了四倍以上，阿尔法 MHC的信使核糖核酸按比例减少。因此，表型， 生物物理和生化心肌收缩功能随年龄增长的变化 至少在一定程度上受转录调控。

Cardiac cell enlargement occurs in response to chronic arterial pressure overload in young rodents and with advanced adult age in normotensive rodents. Cardiac muscle of both senescent and pressure overloaded hearts exhibit a nearly identical pattern of altered cardiac excitation-contraction mechanisms, among which are a reduced contraction velocity, a reduction in the myosin ATPase activity, a marked increase in the expression of the V,(beta myosin heavy chain, MHC) and a reduction in V1 (alpha MHC) isoforms. In the heart of younger hypertensive adult rodents, this shift in MHC isoforms is due, in part at least, to changes in transcription of beta and alpha MHC genes. The present study was undertaken to determine whether the marked MHC shift occurring with age between adulthood and senescence is also associated with changes in MHC gene expression. Levels of mRNA coding for alpha and beta MHC were determined by Northern analysis and dot blots (oligonucleotide probes on pooled RNA purified from 6 hearts each of animals of a broad age range. The mRNA for beta MHC increased greater than fourfold from 1 to 24 months, the alpha mRNA for a MHC decreased by a proportional amount. Thus, the phenotypic, biophysical and biochemical cardiac contractile changes with adult aging are, in part at least, transcriptionally regulated.