Microparticles are vesicles (0.1 – 1µm in size) from the plasma membrane that are shed from apoptotic or stressed cells. They have been shown to be present at increased levels in various pathological states, including diabetes and cardiovascular disease. Additionally, they have been shown to have a role in vascular endothelial function.Endothelial cells and nitric oxide are important partners in vascular health. Nitric oxide is crucial to preventing the development of neointimal hyperplasia, a process that occurs following arterial injury, and develops even more aggressively in type 2 diabetes. Recent evidence has shown that endothelial microparticles are increased in a type 2 diabetic state and may impair endothelial function in vitro. To our knowledge, there are no studies that have investigated the role microparticles play in the development of neointimal hyperplasia and nitric oxide. We hypothesize that there will be elevated levels of endothelial microparticles in type 2 diabetes and that application of nitric oxide after carotid balloon injury will significantly decrease endothelial microparticle levels. Thus, the aims of this proposal are to: 1) evaluate endothelial microparticle levels in different diabetic rodent models after carotid artery injury, 2) ascertain if endothelial microparticle levels correlate to the amount of neointimal hyperplasia in non-diabetic, type 1 diabetic, and type 2 diabetic rodents, and 3) determine if levels of endothelial microparticles change with application of nitric oxide after carotid injury. It is well known that diabetes is a worldwide epidemic and that this disease process leads to many deleterious effects. Understanding microparticles' exact function may lead to the development of novel therapies to treat vascular disease, or to the development of screening assays for endothelial dysfunction, thereby allowing for earlier intervention. Therefore, elucidation of the function and relevance of microparticles in vascular disease states is of utmost importance toward improving patient care.
|Effective start/end date||3/1/13 → 2/28/14|
- American Medical Association Foundation (Seed Grant Agreement 2013-2014)