APOLIPOPROTEIN A AND ATHEROSCLEROSIS IN YOUTH

载脂蛋白 A 与青年动脉粥样硬化

• 批准号: 2226747
• 负责人: David L. Rainwater
• 金额: $ 6.08万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226747
• 关键词: SDS polyacrylamide gel electrophoresis; adolescence (12-20); age difference; apolipoproteins; atherosclerosis; atherosclerotic plaque; blood chemistry; blood lipid; cholesterol; disease /disorder proneness /risk; histopathology; human tissue; molecular weight; phenotype; postmortem; protein isoforms; racial /ethnic difference; tobacco abuse; western blottings; young adult human (21-34)

The lipoprotein Lp(a) is strongly associated with measures of atherosclerosis and cardiovascular disease. In several studies, primarily of white populations, Lp(a) was found to be the strongest correlate with disease. The unique apolipoprotein, apo(a), must play an essential role in the association because it is the only lipoprotein component that distinguishes Lp(a) from low-density lipoprotein (LDL). Lp(a) exhibits extremely wide ranges of variation between individuals in serum concentrations and in the sizes of apo(a), but both are quite constant during an individual's lifetime. Apo(a) size phenotypes show significant differences among populations, including blacks and whites. We hypothesize that apo(a) size variation is correlated with extent and severity of arteriosclerotic lesions. We plan to test this hypothesis using serum samples taken at autopsy of young persons, 15-34 years of age, who have died of external causes. These samples come from the multicenter study funded by two initiatives entitled Pathobiological Determinants of Atherosclerosis in Youth (PDAY) and Risk Factors in Early Human Atherosclerosis (RFEHA). In the proposed study we will measure apo(a) phenotypes in serum samples from approximately 715 PDAY-RFEHA cases. The end point in this study will be the measures of extent and severity of atherosclerosis as determined by pathologists in the study. The Specific Aims are as follows: 1) to determine apo(a) isoform phenotypes (molecular weights) in serum samples from approximately 715 PDAY-RFEHA cases; 2) to quantitate relative amounts of each band for all samples with two distinguishable apo(a) isoform bands; 3) to determine the association of apo(a) molecular weight with extent and severity of lesions after accounting for the effects of Lp(a), lipoprotein cholesterol, smoking, race, gender, and age; and 4) to determine the effects of race and gender on the association of apo(a) molecular weight with extent and severity of lesions. The results of this study will be used to test the hypothesis that variation in apo(a) size phenotype is associated with prevalence of atherosclerotic lesions. The potential long-term benefit to human health will be the identification of high risk phenotypes that warrant clinical intervention.

脂蛋白Lp（a）与以下指标密切相关： 动脉粥样硬化和心血管疾病。在一些研究中，主要 在白色人群中，Lp（a）与 疾病独特的载脂蛋白，载脂蛋白（a）， 因为它是唯一的脂蛋白成分， 将Lp（a）与低密度脂蛋白（LDL）区分开来。Lp（a）证物 血清中个体间的变异范围极广 载脂蛋白（a）的浓度和大小，但两者都是相当恒定的 在一个人的一生中。 载脂蛋白（a）大小表型显示显著 不同的种族，包括黑人和白人。我们假设 载脂蛋白（a）的大小变化与 动脉病变我们计划用血清来验证这个假设 对15-34岁的年轻人进行尸检时采集的样本， 死于外部原因。这些样本来自多中心研究 由两项名为“艾滋病毒/艾滋病的病理生物学决定因素”的倡议资助， 青年动脉粥样硬化（PDAY）和早期人类的危险因素 动脉粥样硬化（RFEHA）。 在拟议的研究中，我们将测量载脂蛋白（a） 来自大约715例PDAY-RFEHA病例的血清样品中的表型。的 本研究的终点将是测量 动脉粥样硬化，由病理学家在研究中确定。具体 目的如下：1）测定载脂蛋白（a）亚型表型（分子生物学）， 重量）; 2）至 用两种方法定量所有样品中每个条带的相对量 可区分的载脂蛋白（a）亚型条带; 3）确定 载脂蛋白（a）分子量与病变的范围和严重程度 考虑到Lp（a）、脂蛋白胆固醇、吸烟、 种族、性别和年龄; 4）确定种族和性别的影响 载脂蛋白（a）分子量与 病变本研究的结果将用于检验假设 载脂蛋白（a）大小表型的变异与 动脉粥样硬化病变对人类健康的潜在长期益处 将是识别高风险表型， 干预