The Role of Scavenger Receptor Class B Type 1 in Humans

B 型清道夫受体 1 在人类中的作用

• 批准号: 8277901
• 负责人: Annabelle Rodriguez
• 金额: $ 20.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2012-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277901
• 关键词: Actins; Acylation; Adrenal Glands; Affect; African American; Alleles; Asians; Atherosclerosis; Biological Assay; Blood; Blood specimen; Body mass index; Cardiovascular Diseases; Cardiovascular system; Caucasians; Caucasoid Race; Cell membrane; Cells; Chemicals; Cholesterol; Cholesterol Esters; Code; DNA; Data; Docking; Endothelial Cells; Event; Female; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Haplotypes; Heart Diseases; Hepatocyte; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hispanics; Human; Hydroxyl Radical; In Vitro; Infertility; Knockout Mice; Lipids; Lipoprotein Receptor; Lipoproteins; Low-Density Lipoproteins; Measurement; Measures; Mediating; Messenger RNA; Minor; Mus; Myocardial Infarction; Outcome; Ovary; Participant; Particle Size; Persons; Plasma; Plasmids; Population; Primer Extension; Protein Deficiency; Proteins; RNA; Radiolabeled; Recruitment Activity; Regression Analysis; Research Project Grants; Risk; Role; SR-B proteins; SR-BI receptor; Sample Size; Sampling; Specific qualifier value; Structure; Testing; Testis; Tissues; Translations; Variant; Very low density lipoprotein; Western Blotting; base; cardiovascular disorder risk; cohort; high density lipoprotein receptor; inflammatory marker; insight; interest; macrophage; macrophage scavenger receptors; monocyte; premature; promoter; protein expression; protein function; public health relevance; radiotracer; receptor expression; receptor function; research study; translation assay; uptake

DESCRIPTION (provided by applicant): High density lipoprotein cholesterol (HDL-C) levels are thought to protect against cardiovascular disease. This may or may not be true in certain populations. The long-term goal of this research project is to determine if a deficiency in the lipoprotein receptor, scavenger receptor class B type I or SR-BI, is a cause of high levels of HDL-C and, perhaps paradoxically, an increased risk for cardiovascular disease. In specific aim 1, we will perform in vitro experiments to examine the mechanism(s) by which certain SR-BI gene (SCARB1) variants affect SR-BI protein expression. In specific aim 2, we will continue recruiting subjects with HDL-C levels above 60 mg/dl (this is because levels above 60 mg/dl are thought to be cardioprotective) and obtaining blood specimens to measure cholesterol levels, DNA, and monocyte-derived macrophage that express SR-BI protein. We will examine the association of genetic variations within the SCARB1 gene with lipid levels, macrophage SR-BI protein and RNA expression and SR-BI function (as measured by the uptake of cholesteryl esters from radiolabeled HDL). We will also examine the association of SCARB1 polymorphisms and lipid levels and subclinical atherosclerosis in participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and in subjects with premature myocardial infarction (Myocardial Infarction Genetics Consortium Study). The results from our studies will provide further insight into the role of SR-BI on lipid levels and cardiovascular disease in subjects with elevated levels of HDL-C, in a larger population (MESA) well-represented by persons of Caucasian, African-American, Hispanic and Asian ancestry, and in subjects with premature myocardial infarction. PUBLIC HEALTH RELEVANCE: High density lipoproteins (HDL) are considered the "healthy" or "good" fraction of the blood cholesterol levels. However, heart disease can occur despite a person having desirable levels of HDL. Our study will examine whether variations in the gene for the HDL receptor, scavenger receptor class B type I or SR-BI, might be associated with good levels of HDL and heart disease.

描述（由申请人提供）：高密度脂蛋白胆固醇（HDL-C）水平被认为可以预防心血管疾病。在某些人群中，这可能是不正确的。该研究项目的长期目标是确定脂蛋白受体（清道夫受体I类或SR-BI）的缺乏是否是高水平HDL-C的原因，并且可能矛盾地增加了心血管疾病的风险。在特定目标1中，我们将进行体外实验，以检查某些SR-BI基因（Scarb1）变体影响SR-BI蛋白表达的机制。在特定目标2中，我们将继续招募HDL-C水平高于60 mg/dL的受试者（这是因为认为高于60 mg/dl的水平被认为是心脏保护的），并获得血液标本以测量表达SR-BI蛋白的胆固醇水平，DNA和单核细胞衍生的巨噬细胞。我们将研究Scarb1基因中的遗传变异与脂质水平，巨噬细胞SR-BI蛋白和RNA表达和SR-BI功能的关联（通过从放射性标记的HDL中摄取胆固醇酯的摄取来测量。我们还将研究疤痕1多态性与脂质水平以及亚临床动脉粥样硬化在多族裔动脉粥样硬化研究（MESA）以及心肌梗死（心肌梗死遗传联盟研究）的受试者中的关联。我们研究的结果将进一步洞悉SR-BI对HDL-C水平升高的受试者的脂质水平和心血管疾病的作用，在较大的人群（MESA）中，由高加索人，非裔美国人，西班牙裔，西班牙裔和亚洲祖先和受试者及其过早的肌电量。 公共卫生相关性：高密度脂蛋白（HDL）被认为是血液胆固醇水平的“健康”或“良好”部分。但是，尽管有理想水平的HDL水平，但仍会发生心脏病。我们的研究将检查HDL受体（清道夫受体I类或SR-BI）基因的变化是否可能与良好的HDL和心脏病有关。