Role of Endothelial Function in SCI CVD Risk

Description

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.