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：
7799189
负责人：
RALPH GREEN
金额：
$ 36.35万
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 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7799189
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 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 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 Pulmonary Hypertension Pyridoxal Phosphate Quality of life Recruitment Activity Research Research Design Research Personnel Risk Risk Factors Role Scientist Severities Sickle Cell Sickle Cell Anemia Spleen 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 improved in vivo innovative technologies intravital microscopy meetings minimal risk morphometry mortality patient population 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（申请人提供）：镰状细胞病（SCD）的特点是急性临床表现，包括疼痛危象、急性胸部综合征、阴茎异常勃起和中风，以及对心、肺、肾、眼、脾的慢性不可逆损害和股骨头。血管损伤和闭塞主要影响微血管系统，是大多数并发症的根源。成人和儿童镰状细胞病患者的另一个特征是低维生素 B6 状态的患病率很高（超过 50%），如血浆 5'-磷酸吡哆醛水平低（<20 nmol/L）所示。 B6 缺乏是普通人群心血管疾病、外周血管疾病和中风的危险因素，但尚不清楚低 B6 状态是否会影响 SCD 患者的血管发病率。我们实验室的初步数据表明，低 B6 状态与介导红细胞和白细胞粘附到血管内皮的粘附分子循环水平增加有关，这是 SCD 患者血管闭塞发病机制中的关键事件。因此，该提案的长期目标是检验 SCD 患者补充维生素 B6 将降低粘附分子水平并改善血管功能的假设。具体目标是 1) 评估 SCD 患者 B6 状态、血管粘附分子以及微血管形态和功能之间的横截面关系，2) 评估 B6 补充剂对同一患者这些参数的影响。使用标准血液学测量来表征成人和儿童 SCD 患者，将在基线时评估 5'-磷酸吡哆醛、已知与血管损伤相关的可溶性粘附分子（通过实时多重测定）和血流的血液水平速度和微血管形态测量（通过直接实时计算机辅助活体显微镜）。为了检验维生素 B6 补充剂将改善微血管形态和血流量并降低循环粘附分子水平的假设，这些患者将使用双盲、安慰剂对照研究设计接受为期一年的维生素 B6 补充剂治疗。干预期间每三个月重复测量 B6 状态、粘附分子水平和微血管特征。 SCD 的血管并发症对这些患者的发病率、死亡率和生活质量具有重大负面影响。补充维生素对健康产生积极影响，可以改善与这种疾病相关的高发病率和死亡率，有可能以最小的成本和风险带来高效益。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Indicators for assessing folate and vitamin B12 status and for monitoring the efficacy of intervention strategies.

用于评估叶酸和维生素 B12 状态以及监测干预策略有效性的指标。

DOI：
发表时间：
2008-06
期刊：
影响因子：
1.9
作者：
Green; Ralph
通讯作者：
Ralph

Exchange transfusion therapy and its effects on real-time microcirculation in pediatric sickle cell anemia patients: an intravital microscopy study.

换血疗法及其对儿童镰状细胞贫血患者实时微循环的影响：一项活体显微镜研究。

DOI：
发表时间：
2012-04
期刊：
影响因子：
0
作者：
Cheung, Anthony T W;Miller, Joshua W;Miguelino, Maricel G;To, Wilson J;Li, Jiajing;Lin, Xin;Chen, Peter C;Samarron, Sandra L;Wun, Ted;Zwerdling, Theodore;Green, Ralph
通讯作者：
Green, Ralph

Multiplexed measurements of immunomodulator levels in peripheral blood of healthy subjects: Effects of analytical variables based on anticoagulants, age, and gender.

健康受试者外周血中免疫调节剂水平的多重测量：基于抗凝剂、年龄和性别的分析变量的影响。

DOI：
发表时间：
2014-11
期刊：
影响因子：
0
作者：
Krishnan, V V;Ravindran, Resmi;Wun, Ted;Luciw, Paul A;Khan, Imran H;Janatpour, Kim
通讯作者：
Janatpour, Kim

Homocysteine is associated with severity of microvasculopathy in sickle cell disease patients.

同型半胱氨酸与镰状细胞病患者微血管病变的严重程度相关。

DOI：
发表时间：
2020
期刊：
影响因子：
6.5
作者：
Samarron, Sandra L;Miller, Joshua W;Cheung, Anthony T;Chen, Peter C;Lin, Xin;Zwerdling, Theodore;Wun, Ted;Green, Ralph
通讯作者：
Green, Ralph