Vascular Protection in Hibernating Woodchucks

冬眠土拨鼠的血管保护

• 批准号: 9020511
• 负责人: STEPHEN F VATNER
• 金额: $ 45.47万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9020511
• 关键词: Address; Animal Model; Animals; Attenuated; Blood Circulation; Blood Vessels; Blood flow; Cause of Death; Chronic; Coronary; Coronary Arteriosclerosis; Coronary Vessels; Coronary artery; Cyclic AMP-Responsive DNA-Binding Protein; Data; Development; Exhibits; Experimental Animal Model; Experimental Models; Food; Growth; Heart failure; Hibernation; Infarction; Ischemia; Mammals; Measures; Mediating; Mind; Modeling; Molecular; Mus; Myocardial; Myocardial Ischemia; Myocardial Reperfusion; Nitric Oxide Synthase; Oxygen Consumption; Play; Population; Reperfusion Injury; Role; Signal Pathway; Stress; Time; Water; Woodchuck; angiogenesis; coronary artery occlusion; disability; mouse model; novel; novel therapeutics; public health relevance; receptor; response

 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.

 描述（由申请人提供）：当没有食物和水时，哺乳动物冬眠是一种独特且有效的生存策略。我们的假设是，用于抵御冬季压力的一些机制也可能用于保护。尽管冬眠哺乳动物没有冠状动脉疾病或心肌缺血，但该提案的重点是检查土拨鼠在冬季对冠状动脉完全闭塞的保护作用及其后果。冠状动脉完全闭塞后，改善缺血影响的主要机制与冠状血管和血管生成的发展有关，我们的初步数据支持了这一点。还表明，血管硬度和血管成分在冬季发生变化，从而增强了血流，因此保持 cAMP 反应元件结合蛋白 (CREB) 和一氧化氮合酶 (NOS) 等潜在细胞机制非常重要。请注意，这些研究将首次在自然的心脏保护模型中进行，这与实验动物模型或基因改造小鼠的传统研究截然不同。我们的假设：土拨鼠通过开发广泛改变其血管的机制来为冬天做好准备。减少血管硬度并诱导新的冠状血管，为缺血性心脏提供血流并减轻慢性、完全动脉冠状动脉闭塞后心力衰竭的发展和重塑。