Angiogenesis and Mechanisms of Exercise Training in PAD

PAD 的血管生成和运动训练机制

• 批准号: 7340803
• 负责人: BRIAN H ANNEX
• 金额: $ 8.04万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-25 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7340803
• 关键词: Academic Medical Centers; Accounting; Activities of Daily Living; Address; Aerobic Exercise; Affect; Age; Age-Years; Angioplasty; Ankle; Antiplatelet Drugs; Apoptosis; Appendix; Atherosclerosis; Blood Pressure; Blood Vessels; Blood capillaries; Blood flow; Bypass; Cardiac; Cardiovascular system; Caring; Cell Death; Cell Respiration; Cerebrovascular Disorders; Class; Clinical; Clinical Research; Colorado; Complement component C1s; Condition; Data; Disease; Doctor of Medicine; Endothelial Cells; Ensure; Evaluation; Exercise; Functional disorder; Gender; Goals; Growth; Growth Factor; Health; Health Sciences; Heart; Heart failure; High Prevalence; Home environment; Impairment; Intermittent Claudication; Investigation; Leg; Lower Extremity; Measurement; Measures; Mediating; Medical; Modality; Modeling; Modification; Molecular; Morbidity - disease rate; Muscle; Muscle Fibers; New York; Numbers; Obesity; Operative Surgical Procedures; Outcome; Oxygen; Oxygen Consumption; Pain; Pain-Free; Patients; Performance; Perfusion; Peripheral arterial disease; Persons; Pharmacotherapy; Physical activity; Physiological; Play; Plethysmography; Population; Prevalence; Principal Investigator; Process; Quality of life; Randomized; Randomized Controlled Clinical Trials; Rate; Recruitment Activity; Reporting; Research Personnel; Rest; Risk; Risk Factors; Role; Sample Size; Sex Characteristics; Skeletal Muscle; Specificity; Stem cells; Stimulus; Structure; Supervision; Testing; Therapeutic; Time; Tissues; Training; Treadmill Tests; Treatment Protocols; Universities; Vascular Endothelium; Walking; Week; Woman; angiogenesis; artery occlusion; base; brachial artery; capillary; claudication; density; disorder control; health related quality of life; hemodynamics; improved; indexing; insight; men; mortality; novel; prescription document; prescription procedure; programs; response

Peripheral arterial disease (PAD) impairs arterial blood flow to the legs & is a major indicator of systemic atherosclerosis. PAD affects 5% of the US population over 50. Approx 1/3 of patients with PAD have typical claudication, defined as pain in one or both legs on walking, that is relieved by rest. Patients with claudication have a marked impairment in exercise performance similar to patients with NYHA class III heart failure. Goals of treatment for PAD patients include risk-factor modification & antiplatelet drug therapy to address increased cardiovascular mortality risk. Supervised exercise training is the most efficacious treatment to improve walking capacity, demonstrated in many (small) randomized trials. Neither the pathophysiology of claudication nor the mechanism(s) by which exercise training improves walking times in persons with IC are completely understood. It is unknown how long-term exercise training affects skeletal muscle or to what extent skeletal muscle abnormalities in PAD are reversible. Women have been largely underrepresented in mechanistic studies of IC and exercise training. There is an urgent need for clinical research directed towards defining the basis of the exercise training changes induced in PAD patients in order to: 1) provide insights into the general pathophysiology of the exercise impairment in PAD; 2) permit scientifically plausible & testable modifications to currently prescribed exercise regimens to better employ this critical therapeutic modality &, 3) identify novel targets from pharmacotherapy that are capable of inducing the repertoire of molecular responses induced by exercise training. In this RFA (HL-03-003) (AMNESTI in PAD), men & women (n=160), over 40 years, with IC & an ankle/brachial systolic blood pressure ratio (ABI) <0.8 at rest, will be recruited from Duke Univ Med Ctr and the Univ of Colorado Health Sci Ctr. Patients will be randomized to a supervised or home-based exercise program. Evaluations will be at baseline, 3-weeks (super vised exercise) and 3-months. Age-gender matched healthy controls (n=66) will be tested at base line. The central hypothesis is that the beneficial effects of exercise training are primarily mediated through an angiogenic effect. Sp Aim 1 will establish the baseline vascular abnormalities present in patients. Sp Aim 2 will establish the ability of the selected vascular abnormalities in Sp Aim I to pre- dict peak oxygen consumption in PAD using a prediction model. Sp Aim 3 will establish the ability of exercise training to modify the vascular abnormalities in PAD. Sp Aim 4 will examine the gender specificity of the results obtained in Sp Aim 1-3.

周围动脉疾病（PAD）会损害腿部的动脉血流，是全身的主要指标 动脉粥样硬化。 PAD影响5％以上的美国人口的5％。大约1/3的PAD患者患有 典型的lauti脚，被定义为行走时一条或两条腿的疼痛，这可以缓解休息。患者 lau不休的运动表现有明显的损害，类似于NYHA III类心脏的患者 失败。 PAD患者的治疗目标包括风险因素修饰和抗血小板药物治疗 解决心血管死亡率增加的风险增加。监督运动训练是最有效的治疗方法 为了提高步行能力，在许多（小）随机试验中证明。没有病理生理学 lautain或锻炼训练改善IC人步行时间的机制是 完全理解。尚不清楚长期运动训练如何影响骨骼肌肉或什么 PAD中骨骼肌异常的程度是可逆的。妇女在很大程度上不足 IC和运动训练的机械研究。迫切需要针对的临床研究 定义PAD患者引起的运动训练更改的基础：1） 运动障碍的一般病理生理学； 2）允许科学合理且可测试 修改当前规定的运动方案，以更好地采用这种关键的治疗方式和 3）从药物疗法中确定能够诱导分子曲目的新靶 运动训练引起的反应。在此RFA（HL-03-003）（板块中的amnesti）中，男性和女人 （n = 160），超过40年，静止时有IC＆A脚踝/臂收缩压比（ABI）<0.8，将为 从杜克大学Med CTR和Colorado Health Sci CTR的大学招募。患者将被随机分为 监督或家庭锻炼计划。评估将在基线，3周（超级访问 运动）和3个月。年龄性别匹配的健康对照（n = 66）将在基线测试。中央 假设是运动训练的有益作用主要是通过血管生成作用介导的。 SP AIM 1将建立患者存在的基线血管异常。 SP AIM 2将确定 SP AIM I中选定的血管异常的能力，可以使用PAD中的峰值消耗量 预测模型。 SP AIM 3将建立运动训练的能力，以改变血管异常 在垫子中。 SP AIM 4将检查SP AIM 1-3中获得的结果的性别特异性。