Role of Vascular Endothelial Function After Spinal Cord Injury Related Cardiovascular Disease Risk
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Association of Endothelial cell-derived microvesicles to Endothelium-dependent vasodilation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: Brachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid) (Procedure)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: Acetylcholine (Drug)
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: venous occlusion plethysmography (Procedure)
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: Acetylcholine (Drug)
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: Sodium Nitroprusside (Drug)
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: Ascorbic acid (Drug)
Spinal Cord Injury
Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury [NLI] at T2 or below).
干预措施: venous phlebotomy (Procedure)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: Brachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid) (Procedure)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: venous occlusion plethysmography (Procedure)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: Sodium Nitroprusside (Drug)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: Ascorbic acid (Drug)
Control (Non-Spinal Cord Injury)
Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.
干预措施: venous phlebotomy (Procedure)
结局指标
主要结局
Association of Endothelial cell-derived microvesicles to Endothelium-dependent vasodilation
时间窗: Baseline
Endothelium-dependent vasodilation
时间窗: Measured at baseline (without acetylcholine) and immediately after each acetylcholine dose for 3-5 minutes.
Total forearm blood flow with be measured by strain gauge venous plethysmography under baseline conditions and under pharmacological manipulation with acetylcholine at increasing concentrations (8, 16, 32ug/ml).
Endothelium-independent vasodilation
时间窗: Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.
Total forearm blood flow with be measured by strain gauge venous plethysmography under baseline conditions and under pharmacological manipulation with sodium nitroprusside at increasing concentrations (1, 2, 4ug/ml).
Endothelial cell-derived microvesicles concentration
时间窗: Baseline
Endothelial cell-derived microvesicles will be collected from venous blood samples and counted used flow cytometry to determine a circulating concentration.
Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells nitric oxide bioavailability
时间窗: Baseline
Endothelial cell-derived microvesicles will be sorted and collected by fluorescence-activated cell sorting (FACS) flow cytometry. The endothelial cell-derived microvesicles will be co-cultured with human coronary artery endothelial cells. Endothelial Nitric Oxide Synthase and phosphorylation sites of interest will be measured by intracellular protein expression quantification of whole cell lysates by capillary electrophoresis immunoassays. Nitric oxide production will be assessed by total nitric oxide and nitrate/nitrite parameter assays.
Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells reactive oxygen species and antioxidant capacity
时间窗: Baseline
Endothelial cell-derived microvesicles will be sorted and collected by fluorescence-activated cell sorting (FACS) flow cytometry. The endothelial cell-derived microvesicles will be co-cultured with human coronary artery endothelial cells. Super oxide dismutase and catalase expression will be measured by intracellular protein expression quantification of whole cell lysates by capillary electrophoresis immunoassays. Intracellular oxidative stress will be assessed by ROS-Glo H2O2 assay.
次要结局
未报告次要终点