UCSF Living Heart Resource

描述（由申请人提供）： 目前有500万美国人被诊断患有心力衰竭，每年有55万新病例。心力衰竭由于机械功能障碍本身以及心律失常而导致显著的发病率和死亡率。旨在研究兴奋收缩偶联和心律失常底物的调节（和失调）机制的人类研究是有限的，并且目前在动物与人类中已知的心血管疾病和心律失常之间存在很大的差距。该提案试图通过创建一个获取可行的人类衰竭和非衰竭心脏的系统来缩小这一差距，然后将组织和细胞快速分配给研究人员进行需要“活”准备的实验。本基金中提出的具体目标旨在：1）开发基础设施，以快速获取、保存和分发用于生理学研究的人类心脏; 2）提供保存的人类心脏组织资源，以支持几位研究者正在进行的需要“活”人类心脏组织的电生理学和机械功能研究。为了实现这些目标，我们将开发一个“随叫随到”的组织收集系统，招募和培训收集组织所需的人员，以保持活力，并将有活力的组织分发给研究人员进行实验。此外，将开发一个基于网络的数据库，以确定需要组织的研究人员，能够通知这些研究人员组织可用，并提供有关组织的背景信息。通过获得可行的失败和非失败的人类心脏，几个领域将与假设驱动的研究。这些领域包括：心律失常的机制、心脏组织的电生理特性、肾上腺素能受体和信号转导、连接蛋白表达和运输、细胞内钙处理和患病心脏的心室功能。在加州大学系统内有几个实验室，包括UCSF和UC Davis，进行这些领域的心血管研究，这些研究将受益于获得有活力的人体组织的能力。这项研究将能够描绘心血管研究的广泛进展，因为第一次，几个假设驱动的研究将能够使用人体组织进行。 公共卫生相关性：心力衰竭在美国是一个重要的健康问题，大多数关于心力衰竭和与之相关的其他心血管问题的知识来自动物研究。有了这笔赠款，我们将能够继续开发人类心脏组织资源，供研究人员进行实验，以进一步了解这些心血管问题的机制。

DESCRIPTION (provided by applicant): There are currently 5 million Americans with diagnosed heart failure, and 550,000 new cases every year. Heart failure causes significant morbidity and mortality from the mechanical dysfunction itself as well as from arrhythmias. Human studies aimed at studying the mechanisms of regulation (and dysregulation) of excitation contraction coupling and arrhythmia substrates are limited, and currently there is a large gap between what is known about cardiovascular diseases and arrhythmias in animals as opposed to humans. This proposal attempts to close this gap by creating a system of acquiring viable human failing and non-failing hearts and then quickly distributing the tissue and cells to researchers to perform experiments requiring "live" preparations. The Specific Aims that are proposed in this grant are designed to 1) develop the infrastructure to rapidly procure, preserve and distribute explanted human hearts for physiologic studies; 2) To provide a resource of preserved human cardiac tissue to support several ongoing studies in electrophysiology and mechanical function requiring "live" human cardiac tissue by several investigators. In order to achieve these aims, we will develop an "on call" system of tissue collection, recruit and train the personnel needed to collect the tissue such that viability is maintained, and distribute viable tissue to researchers for experiments. In addition, a web based database will be developed to identify researchers needing tissue, be able to notify those researchers that tissue is available, and provide background information about the tissue. By obtaining viable failing and non-failing human hearts, several areas will be addressed with hypothesis driven research. These areas include: mechanisms of cardiac arrhythmias, electrophysiological properties of cardiac tissue, adrenergic receptors and signal transduction, connexin expression and trafficking, intracellular calcium handling, and ventricular function in diseased hearts. There are several laboratories within the University of California system including UCSF and UC Davis performing these areas of cardiovascular research that would benefit from having the ability to acquire viable human tissue. This research will be able to paint a broad stroke of advancement in cardiovascular research as for the first time,several hypothesis driven studies will be able to be performed using human tissue. PUBLIC HEALTH RELEVANCE: Heart failure is a significant health issue in the United States, and most of what is known about heart failure and the other cardiovascular problems that are associated with it has come from animal studies. With this grant we will be able to continue to develop a resource of human heart tissue for investigators to perform experiments to further understand the mechanisms of these cardiovascular problems.