AGING OF THE HEART--GENDER DIFFERENCES

心脏老化——性别差异

• 批准号: 6132480
• 负责人: YUK-CHOW NG
• 金额: $ 7.83万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6132480
• 关键词: aging; apoptosis; calcium flux; cardiac myocytes; gender difference; heart function; heart ventricle; hemodynamics; laboratory rat; muscle contraction; muscle stress; terminal nick end labeling

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.

该项目的长期目标是阐明 心肌老化的性别差异。初步结果显示， 心肌重构和SR Ca 2 +-ATP酶表达的差异 雄性和雌性F344/BN大鼠之间的差异。拟议 项目将研究以下目标：1）：假设将被检验 随着年龄的增长，雄性F344 B/N大鼠的心功能失代偿。 比雌性大鼠更大的程度，女性心脏经历更同心 比男性的心脏更容易重塑体内心脏功能和心室形态 将被研究。针对不同性别的适应措施的基本机制将是 通过研究肌细胞缩短、Ca2+动力学和程序化细胞来检查， 死亡这些研究的结果将有助于确定 心肌细胞功能障碍与心肌细胞丢失在心肌老化之间的关系 性别2)这一假设将得到验证，在老年女性的心脏， F344/BN大鼠的心脏比雄性大鼠的心脏更能适应应激。我们 假设压力超负荷导致更大的失代偿， 老年雄性大鼠心肌收缩功能和重构的变化明显高于雌性大鼠 大鼠肌细胞大小、细胞缩短、Ca2+动力学和细胞凋亡将在 以阐明潜在的机制。的短期目标 拟议的研究是为了证实和建立衰老的F344/BN大鼠是一个相关的 研究心肌老化性别差异的独特模型， 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性别特异性适应的细胞目标， 帮助制定更好的针对性别的战略， 老年心力衰竭的诊断和治疗。最终目标是 制定干预措施，可能是针对性别的， 心肌老化