Vitamin B6, Vascular Dysfunction and Adhesion Molecules in Sickle Cell Disease

镰状细胞病中的维生素 B6、血管功能障碍和粘附分子

基本信息

批准号：
7263763
负责人：
RALPH GREEN
金额：
$ 36.32万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-15 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7263763
关键词：
Accounting Acute Adhesions Adult Affect Age Aging Anemia Basic Science Biological Assay Blood Blood Flow Velocity Blood Platelets Blood Vessels Blood flow Caliber Cardiovascular Diseases Cell Adhesion Molecules Cerebral Infarction Characteristics Child Childhood Chronic Clinical Computer Assisted Condition Daily Data Dietary Intervention Disease Doctor of Philosophy Double-Blind Method Dysmorphology Erythrocytes Event Eye Functional disorder Future General Population Goals Head Health Heart Hemolysis High Prevalence Injury Intervention Invasive Kidney Kidney Diseases Laboratories Leukocytes Lung Measurement Measures Mediating Medical Research Microcirculation Minority Morbidity - disease rate Morphology Occlusion injury Outcome Measure Pain Pathogenesis Patients Peripheral Vascular Diseases Physicians Placebos Plasma Play Population Priapism Protocols documentation Pyridoxal Phosphate Quality of life Range Recruitment Activity Renal Hypertension Research Research Design Research Personnel Risk Risk Factors Role Scientist Severities Sickle Cell Sickle Cell Anemia Spleen Standards of Weights and Measures Stroke Supplementation Techniques Testing Time Training Translations United States National Institutes of Health Vascular Diseases Vascular Endothelium Vitamin B 6 Deficiency Vitamin B6 Vitamins acute chest syndrome bulbar conjunctiva cost cytokine day improved in vivo innovative technologies intravital microscopy morphometry mortality placebo controlled study

项目摘要

DESCRIPTION (provided by applicant): Sickle cell disease (SCD) is characterized by acute clinical manifestations, including painful crisis, acute chest syndrome, priapism, and stroke, as well as chronic irreversible damage to the heart, lungs, kidneys, eyes, spleen and femoral heads. Vascular injury and occlusion, primarily affecting the microvasculature, underlie most of these complications. Another characteristic of sickle cell patients, both adult and pediatric, is a high prevalence of low vitamin B6 status (exceeding 50%), as indicated by low plasma pyridoxal-5'- phosphate levels (<20 nmol/L). B6 deficiency is a risk factor for cardiovascular disease, peripheral vascular disease, and stroke in the general population, but it is unknown if low B6 status affects vascular morbidity in SCD patients. Preliminary data from our laboratory indicate that low B6 status is associated with increased circulating levels of adhesion molecules that mediate erythrocyte and leukocyte adhesion to the vascular endothelium, key events in the pathogenesis of vascular occlusion in SCD patients. Accordingly, the long- term objective of this proposal is to test the hypothesis that B6 supplements in SCD patients will reduce levels of adhesion molecules and improve vascular function. The specific aims are 1) to assess the cross- sectional relationships between B6 status, vascular adhesion molecules, and microvascular morphology and function in SCD patients, and 2) to assess the effect of B6 supplements on these parameters in the same patients. Adult and pediatric SCD patients, characterized using standard hematological measurements, will be assessed at baseline for blood levels of pyridoxal-5'-phosphate, soluble adhesion molecules known to be related to vascular injury (by real-time multiplex assay), and blood flow velocity and microvessel morphometry (by direct real-time computer-assisted intravital microscopy). To test the hypothesis that B6 supplements will result in improved microvascular morphometry and blood flow associated with a decrease in levels of circulating adhesion molecules, these patients will be treated for one year with vitamin B6 supplements using a double-blind, placebo-controlled study design. Repeat measurements of B6 status, levels of adhesion molecules and microvascular characteristics will be carried out at three-month intervals during the period of intervention. The vascular complications of SCD have a major negative impact on morbidity, mortality, and quality of life for these patients. The positive health impact of vitamin supplementation that could ameliorate the high morbidity and mortality associated with this disorder has the potential for high benefit with minimal cost and risk.

描述（由申请人提供）：镰状细胞疾病（SCD）的特征是急性临床表现，包括痛苦的危机，急性胸部综合征，priapism和中风，以及对心脏，肺，肾脏，眼睛，眼睛，脾和股骨头的慢性不可逆损害。这些并发症大多数是血管损伤和闭塞，主要影响微脉管系统。镰状细胞患者的另一个特征是成人和小儿，是低维生素B6状态（超过50％）的高患病率，如低血浆吡啶还原-5'-磷酸盐水平（<20 nmol/L）所示。 B6缺乏症是心血管疾病，周围血管疾病和中风的危险因素，但尚不清楚B6状态是否影响SCD患者的血管发病率。我们实验室的初步数据表明，低B6状态与循环水平增加有关，这些粘附分子水平介导了血管内皮细胞和白细胞粘附，这是SCD患者血管闭塞发病机理的关键事件。因此，该提案的长期目标是检验以下假设：SCD患者的B6补充剂将降低粘附分子水平并改善血管功能。具体目的是1）评估B6状态，血管粘附分子与微血管形态和功能之间的横断面关系，以及2）评估同一患者中B6补充剂对这些参数的影响。使用标准血液学测量值的成年和小儿SCD患者将在基线时评估吡啶还毒 - 5'-磷酸的血液水平，可溶质粘附分子已知与血管损伤有关（通过实时多路复用测定），以及血流速度和血流速度和微膜片的直接实时计算机化计算机疗法疗法疗法（通过实时多重分析）有关。为了测试B6补充剂将导致与循环粘附分子水平降低相关的微血管形态和血流的假设，使用双盲，安慰剂控制的研究设计将用维生素B6补充剂治疗这些患者一年。重复测量B6状态，粘附分子水平和微血管特征的水平将在干预期间以三个月的间隔进行。 SCD的血管并发症对这些患者的发病率，死亡率和生活质量产生重大负面影响。补充维生素的积极影响，可以改善与这种疾病相关的高发病率和死亡率，从而有可能获得高收益，而成本和风险最低。