Endothelial Function and Peripheral Vein Bypass Graft Remodeling

内皮功能和外周静脉旁路移植物重塑

基本信息

批准号：
8310024
负责人：
Christopher Dean Owens
金额：
$ 12.7万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8310024
关键词：
Accounting Activities of Daily Living Acute Angioplasty Arteries Attenuated Autologous Biological Assay Biological Markers Biological Preservation Biology Blood Circulation Blood Vessels Bypass C-reactive protein Caliber Clinical Coronary Coronary artery Data Dose E-Selectin Endothelium Environment Event Exhibits Failure Functional disorder Gene Expression Healed Histologic Hospitals Human Hydroxymethylglutaryl-CoA Reductase Inhibitors Hyperplasia Implant Inflammation Inflammatory Institutes Interdisciplinary Study Ischemia LDL Cholesterol Lipoproteins Leukocytes Limb Salvage Limb structure Lower Extremity Measurement Measures Mediating Medicine Methodology Methods Molecular Operative Surgical Procedures Outcome P-Selectin Patients Peripheral Pharmacology Phenotype Plasma Process Public Health Schools Randomized Controlled Trials Research Research Personnel Resolution Rho-associated kinase Risk Saphenous Vein Scientist Serum Specimen Surgeon Surrogate Endpoint Technology Testing Thrombomodulin Time Ultrasonography Vasodilation Veins Venous Woman atorvastatin brachial artery clinical epidemiology clinically relevant graft failure graft function graft healing healing hemodynamics human NOS3 protein implantation improved in vivo inflammatory marker insight instructor medical schools monocyte preimplantation programs reconstruction response shear stress

项目摘要

I am an Instructor of Surgery at Harvard Medical School and an Associate Surgeon in the Division of Vascular and Endovascular Surgery at Brigham and Women's Hospital. The following outlines my plan to become an independent clinician-scientist in translational vascular research and a clinical trialist. My proposal capitilizes on the stimulating academic environment and multidisciplinary collaborations engendered by Harvard Medical School, Harvard School of Public Health, and Massachussetts Institute of Technology. Many patients with PAD progress to critical limb ischemia. Autologous vein remains the most durable conduit for bypass surgery, yet failure rates remain significant (30-50% over 5 years). I have previously shown that these patients have a distinct inflammatory phenotype as assessed by C-reactive protein (CRP). Moreover, elevated baseline CRP levels are predictive of adverse cardiovascularand vein graft-related events after peripheral bypass surgery. Bypass grafts in patients with elevated CRP levels exhibit less adaptive dilation in the first few months after the vein is implanted in the arterial circulation, which portends worse graft function after 1 year. Plasma levels of CRP correlate inversely with brachial and coronary artery endothelial function; however, it is not known if CRP is correlated with vein graft endothelial function. This proposal seeks to elucidate the relationships between endothelial function, inflammation, and vein graft adaptation in the arterial environment. I will determine the relationship between systemic (as assessed by the brachial artery) and vein graft-specific endothelial function to early vein graft remodeling. Endothelial function of the vein will be assessed both in vivo and ex vivo techinques. My second aim is to determine the association between biomarkers of inflammation and endothelial activation with vein graft- specific endothelial function. My final hypothesis is that reducing systemic inflammation by intensive statin therapy (atorvastatin 80 mg) will improve early vein graft adaptation by improving endothelial function. This hypothesis will be tested by a randomized controlled trial of intensive vs conventional dose atorvastatin given in the peri-operative setting. These studies will provide new insights into the understanding of normal and abnormal adaptive processes of human vein graft healing and will have direct clinical relevance by identifying new biomarkers, surrogate endpoints, and mechanisms of existing therapies for vein graft failure.

我是哈佛医学院手术的讲师，也是一名副外科医生 Brigham和妇女医院的血管和血管内手术。以下概述了我的计划成为转化血管研究和临床试验者的独立临床医生科学家。我的提案在刺激的学术环境和多学科合作上委托由哈佛医学院，哈佛公共卫生学院和马萨诸塞州学院发起的技术。许多患有PAD的患者会发展为临界肢体缺血。自体静脉仍然是最大的旁路手术的耐用导管，但失败率仍然显着（在5年内为30-50％）。我有先前表明，这些患者具有通过C反应评估的明显的炎症表型蛋白质（CRP）。此外，升高的基线CRP水平可预测心血管不良和静脉外周旁路手术后与移植物相关的事件。 CRP水平升高的患者的旁路移植物在将静脉植入动脉循环后的头几个月，表现出较少的适应性扩张预示1年后的移植功能较差。 CRP的等离子水平与肱和臂冠状动脉内皮功能；但是，尚不清楚CRP是否与静脉移植物内皮相关功能。该建议旨在阐明内皮功能，炎症和动脉环境中的静脉移植适应。我将确定系统性之间的关系（AS 通过臂动脉）和静脉移植物特异性内皮功能进行评估，以对早期的静脉移植重塑。静脉的内皮功能将在体内和Ex Vivo Techinques中进行评估。我的第二个目标是确定炎症生物标志物与内皮激活与静脉移植物之间的关联特定的内皮功能。我最后的假设是通过强化他汀类药物减少系统性炎症治疗（Atorvastatin 80 mg）将通过改善内皮功能来改善早期静脉移植的适应。这假设将通过对常规剂量atorvastatin进行的随机对照试验进行检验在围手术环境中。这些研究将为对正常和正常的理解提供新的见解人静脉移植物愈合的异常适应性过程，并将具有直接的临床相关性识别新的生物标志物，替代终点和现有静脉移植衰竭疗法的机制。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Assessing drug elution technologies in the superficial femoral artery.

评估股浅动脉的药物洗脱技术。

DOI：
发表时间：
2011
期刊：
Panminerva medica
影响因子：
4.3
作者：
Owens,CD;Gasper,WJ;Conte,MS
通讯作者：
Conte,MS

Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end-stage renal disease.

维生素 D 缺乏与终末期肾病患者的死亡率和不良血管通路结果相关。

DOI：
10.1016/j.jvs.2014.01.037
发表时间：
2014
期刊：
Journal of vascular surgery
影响因子：
4.3
作者：
Walker,JoyP;Hiramoto,JadeS;Gasper,WarrenJ;Auyang,Philip;Conte,MichaelS;Rapp,JosephH;Lovett,DavidH;Owens,ChristopherD
通讯作者：
Owens,ChristopherD

Vein graft failure.