Vascular Protection in Hibernating Woodchucks

 描述(申请人提供)：哺乳动物冬眠是在没有食物和水的冬季生存的一种独特而有效的策略。我们的假设是，一些用于保护冬季应激的机制也可能用于保护缺血心肌，即使冬眠的哺乳动物没有冠状动脉疾病或心肌缺血。这项建议的重点是检查土拨鼠在冬季对冠状动脉完全闭塞的保护及其重塑和心力衰竭发展的后果。在冠状动脉完全闭塞后，改善缺血效应的主要机制与冠状动脉和血管生成的发展有关，这一应用的初步数据支持了这一点。我们的初步数据还表明，血管僵硬和血管成分在冬季会发生变化，从而允许增强血液流动。可能的细胞机制包括cAMP反应元件结合蛋白(CREB)和一氧化氮合酶(NOS)。重要的是要记住，这些研究将第一次在心脏保护的自然模型中进行，与在实验动物模型或转基因小鼠中进行的传统研究截然不同。我们的假设：土拨鼠通过发展广泛修改其血管的机制来为冬天做准备，从而减少血管僵硬和诱导新的冠状动脉血管，从而为缺血的心脏提供血液，并减缓慢性、完全冠状动脉闭塞后心力衰竭的发展和重塑。

 DESCRIPTION (provided by applicant): Mammalian hibernation is a unique and potent strategy for survival in winter when food and water are not available. Our hypothesis is that some of the mechanisms utilized for protection against the stress in winter, might also be used to protect ischemic myocardium, even though hibernating mammals do not have coronary artery disease or myocardial ischemia. The focus of this proposal is to examine the woodchucks' protection in winter against complete coronary artery occlusion and its consequences of remodeling and the development of heart failure. After a complete occlusion of a coronary artery the major mechanism that can ameliorate the effects of ischemia relate to the coronary vessels and development of angiogenesis, which is supported by the preliminary data in this application. Our preliminary data also indicate that vascular stiffness and the composition of vessels are altered in winter thereby permitting enhanced blood flow. Potential cellular mechanisms include cAMP response element-binding protein (CREB) and nitric oxide synthase (NOS). It is important to keep in mind that these studies will be conducted for the first time in a natural model of cardioprotection, quite different from traditional studies in experimental animal models or genetically altered mice. Our Hypothesis: Woodchucks prepare for winter by developing mechanisms that extensively modify their blood vessels resulting in reduced vascular stiffness and induction of new coronary vessels, which provide blood flow to the ischemic heart and attenuate heart failure development and remodeling after chronic, complete coronary artery occlusion.