REGULATION OF CARDIAC MASS IN AORTIC REGURGITATION

主动脉瓣反流中心脏质量的调节

• 批准号: 3472107
• 负责人: NORMAN M MAGID
• 金额: $ 10.17万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472107
• 关键词: antithrombogenic surface; biomaterial development /preparation; biotransformation; blood vessel prosthesis; calcification; cell adhesion; cell migration; chemotaxis; cow; crosslink; elastin; elastomers; extracellular matrix; mechanical stress; peptide chemical synthesis; thermodynamics; vascular endothelium; vascular smooth muscle

The objective of this proposal is to define the alterations in myocardial protein metabolism that regulate the responses to acute and chronic volume overload in an intact animal model of aortic regurgitation. The relative contributions of cardiac protein synthesis and degradation to the structural remodelling that occurs during the development of left ventricular dilatation and eccentric hypertrophy will be examined. The effects of the severity and chronicity of volume overload on synthesis and degradation rates of total cardiac protein, individual myofibrillar proteins and collagen will be investigated. The hypothesis to be tested is that specific and total cardiac protein degradation rates as well as synthesis rates are fundamentally important to the regulation of cardiac protein mass during the left ventricular dilation and eccentric hypertrophy that develop in response to chronic volume overload. Thus we will examine the biochemical mechanisms underlying the structural and functional responses to chronic aortic regurgitation. The process of testing our hypothesis can be expected to improve understanding of cardiac protein regulation in vivo. Specifically, it is hoped that these studies may allow identification of protein metabolic abnormalities that could prove useful as indices of degeneration for timing of valve replacement, or which might provide insights helpful in the design of new therapeutic approaches to retarding the effects of volume loading.

本提案的目的是确定 心肌蛋白质代谢，调节对 急性和慢性容量超负荷的完整动物模型， 主动脉瓣返流 心肌蛋白的相对贡献 合成和降解到结构重塑， 发生在左心室扩张的发展过程中， 将检查离心性肥大。 的影响 合成时容量超负荷的严重程度和慢性程度， 心肌总蛋白、单个肌原纤维 将研究蛋白质和胶原蛋白。 假设是 测试的是，特定和总的心脏蛋白降解率 以及合成速率对生物学的发展至关重要 在左心室期间调节心脏蛋白质质量 扩张和离心性肥大， 慢性容量超负荷 因此，我们将研究生物化学 结构和功能反应的机制 慢性主动脉瓣返流 测试我们的 这一假说有望提高对心脏病的认识， 体内蛋白质调节。 具体而言，希望这些 研究可以识别蛋白质代谢 可以作为退化指标的异常 瓣膜置换术的时机，或可能提供见解 有助于设计新的治疗方法， 容积负荷的影响。