As the American population continues to proportionally age, the impact of cardiovascular disease and diabetes will be a tremendous burden on the healthcare system. Patients with diabetes suffer from higher failure rates of revascularization procedures. The etiology of this failure is driven largely by the development of neointimal hyperplasia which leads to restenosis. Preliminary data from our lab suggest that resident stem cell antigen 1 (Sca-1) progenitor cells may in fact contribute to the developing neointima through phenotypic modulation and terminal differentiation. Yet, little is known about this resident stem cell population in diabetes. Thus, we hypothesize that Sca-1 stem cells contribute to the formation of neointimal hyperplasia after vascular injury in the diabetic environment. Nitric oxide (NO) is an endogenous vasodilator and potent signaling molecule that has been shown to inhibit neointimal hyperplasia in animal models of vascular injury. However no data exist on the relationship between NO and Sca-1 stem cells in a diabetic environment. Therefore, we further hypothesize that NO will inhibit the development of neointimal hyperplasia by regulating the Sca-1 stem cell population. To evaluate the contribution of Sca-1 stem cells to the development of neointimal hyperplasia, we will perform the femoral artery wire injury model of vascular injury in control and diabetic mice with and without periadventitial application of the nitric oxide donor PROLI/NO. We expect that diabetic mice will have increased neointimal hyperplasia and increased Sca-1 expression within the neointima. We expect that NO treatment will drive Sca1 progenitor cells toward a protective endothelial phenotype, thereby inhibiting the development of neointimal hyperplasia in diabetic mice. Our goal is to improve the lives of diabetic patients with cardiovascular disease through high quality and novel, innovative care.
|Effective start/end date||3/1/13 → 2/28/14|
- American Medical Association Foundation (Seed Grant Agreement 2013-2014)
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