AGING OF THE HEART--GENDER DIFFERENCES

拟议项目的长期目标是阐明潜在的机制。 心肌老化的性别差异。初步结果显示 心肌重构与肌浆网钙-ATPase表达的差异 雄性和雌性F344/BN大鼠随着年龄的增长而增加。在建议的 项目将研究以下目标：1)：将检验假设 雄性F344B/N大鼠随着年龄的增长，心功能失代偿。 比雌性大鼠的程度更大，雌性大鼠的心脏更同心 重塑而不是男性心脏。活体心功能和心室形态 将会被研究。针对性别的适应的基础机制将是 通过研究心肌细胞缩短、钙动力学和程序化细胞进行检查 死亡。这些研究的结果将有助于确定 心肌老化过程中心肌细胞功能障碍与心肌细胞丢失的关系 性别。2)这一假设将得到检验，在老年女性的心脏中 与雄性大鼠相比，F344/BN大鼠对应激的适应能力更强。我们 假设压力过载会导致更大的失代偿，就 老年雄性大鼠心肌收缩功能和重构的研究 老鼠。心肌细胞大小、细胞缩短、钙动力学和细胞凋亡 研究以阐明潜在的机制。美国经济的短期目标 建议的研究是确认和确定衰老的F344/BN大鼠是相关的 和独特的模型来研究心肌老化的性别差异，并 开始阐明潜在的机制。拟议研究的结果 可能有助于确定负责特定性别适应的细胞靶点 老年心脏并有助于促进制定更好的针对性别的策略 老年人心力衰竭的诊断和治疗。最终目标是 制定干预措施，这可能是针对性别的，可能会推迟或逆转 心肌老化。

The long-term goal of the proposed project is to elucidate mechanisms underlying gender-related differences in myocardial aging. Preliminary results demonstrated differences in myocardial remodeling and in expression of SR Ca2+-ATPase between male and female F344/BN rats with advancing age. In the proposed project the following objectives will be studied: 1) : The hypothesis will be tested that with advancing age cardiac function in male F344 B/N rats decompensates to. a greater extent than in female rats, and that female hearts undergo more concentric remodeling than male hearts. In vivo cardiac function and ventricular morphology will be studied. Mechanisms underlying gender-specific adaptations will be examined by studying myocyte shortening, Ca2+-dynamics, and programmed cell death. Results from these studies will help to determine the relative importance of myocyte dysfunction vs. myocardial cell loss in myocardial aging between the two genders. 2) The hypothesis will be tested that in advanced age hearts of female F344/BN rats can better adapt to stress compared to hearts of male rats. We postulated that pressure overload causes greater decompensation, in terms of myocardial contractile function and remodeling, in aged male rats than in female rats. Myocyte size, cell shortening, Ca2+-dynamics, and apoptosis will be examined to elucidate the underlying mechanisms. The short-term goal of the proposed study is to confirm and establish that the aging F344/BN rat is a relevant and unique model for studying gender differences in myocardial aging, and to begin elucidating the underlying mechanisms. Results from the proposed studies may help identify cellular targets responsible for gender-specific adaptation of the aged heart and help facilitate development of better gender-specific strategies in diagnosis and treatment of heart failure in the elderly. The ultimate goal is to develop interventions, which may be gender specific, that may delay or reverse myocardial aging.