role of endothelial function in sci cvd risk

Conditions: Spinal Cord Injuries; Cardiovascular Diseases; Endothelial Dysfunction

Summary: individuals with spinal cord injury have heart attacks and strokes more frequently, and much earlier in life. people with spinal cord injuries develop plaque in vessels much faster, and the reasons why are unclear. doctors generally attributed the increased risk with weight gain and developing diabetes, but many studies have shown that even without these common factors, plaque in vessels is developing more often and faster. endothelial cells are a single layer of cells that line all vessels in the body and plays an important role in vessel health. damage to endothelial cells is known to lead to heart attacks and strokes. past studies on endothelial cells of people with spinal cord injury have been unclear. the investigators have new data that these cells are unhealthy after spinal cord injury a measurement. this includes measuring endothelial health by directly altering its function using a catheter in the arm and measuring small particles in blood called endothelial microvesicles. if the project is successful, the investigators will learn important information on the health of endothelial cells after spinal cord injury. the investigators will also be able to use these markers of endothelial cell function to create treatments to improve vessel health and prevent heart attacks and strokes later in life in people with spinal cord injury.

adults with spinal cord injury (sci) demonstrate accelerated atherosclerotic cardiovascular disease (ascvd) occurring \~4 fold more often, and decades earlier in life. importantly, atherosclerosis has been detected in people with sci independent of traditional risk factors, much earlier in life, and appear recalcitrant to conventional risk mitigating inventions such as exercise and diet. also, as disease is silent, many individuals are not screened for this atherosclerotic burden and only aware after the major vascular event of a myocardial infarction or stroke. the mechanisms which drive early ascvd is unknown. endothelial cell dysfunction precedes radiographic or angiographic evidence of atherosclerosis, and plays a central role in the development, progression and severity of atherosclerotic vascular disease. while it has been suggested that sci results in compromised endothelial health, there is little empirical data on the degree or scope of impairment as well as mechanisms underlying any potential impairment. endothelial dysfunction may be an important factor underlying the increased risk and prevalence of ascvd and associated events in adults with sci and a viable target for therapeutic intervention. preliminary data suggests primary endothelial cell impairment related to its vasodilator function and provide potential mechanisms related to oxidative stress burden. the investigators also present the potential of endothelial cell derived microvesicles as a biomarker and mediator of endothelial cell dysfunction. the aim of this proposal is to determine whether endothelial function is impaired in adults with sci. our hypothesis is that endothelium-dependent vasodilation is impaired in adults with sci and oxidative stress and endothelial cell derived microvesicles contribute to this dysfunction. results supporting this hypothesis will: 1) provide mechanistic insight into the excess risk of ascvd in adults with sci; 2) identify therapeutic targets for reducing cardiovascular risk in this population; and 3) provide scientific rationale for vascular-related treatment clinical trials aimed at improving vascular health and reducing cardiovascular risk in individuals with sci.

Eligibility criteria:
inclusion criteria: * men and women of all races, ethnic backgrounds\>18 years of age * traumatic spinal cord injury (sports, assault, transport, fall, other traumatic causes) * time since injury (\> 12 months) * paraplegia motor complete injury (neurological level of injury at t2 or below, asia impairment scale a or b exclusion criteria: * history of high blood pressure * history cardiovascular disease (coronary artery disease, congestive heart failure, myocardial infarction, cerebrovascular accident). * history high cholesterol * history of diabetes type i or type ii * history of obstructive pulmonary disease * history of chronic kidney or liver disease * history of cancer * history of autoimmune disease (thyroid disease, lupus, rheumatoid arthritis, etc). * history of smoking tobacco in the last 12 months * history of alcohol use