Vascular Protection in Hibernating Woodchucks

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 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.