APOLIPOPROTEIN A AND ATHEROSCLEROSIS IN YOUTH

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，主要是 在白人群体中，Lp(A)与 疾病。独特的载脂蛋白apo(A)必须在 这种联系是因为它是唯一的脂蛋白成分 Lp(A)与低密度脂蛋白(LDL)的区别。Lp(A)证物 血清中个体间极大范围的变异 浓度和载脂蛋白(A)的大小，但两者都相当恒定 在一个人的一生中。载脂蛋白(A)大小表型显著 不同人群之间的差异，包括黑人和白人。我们假设 载脂蛋白(A)的大小变化与疾病的程度和严重程度相关。 动脉硬化性病变。我们计划用血清来检验这一假说 对15-34岁的年轻人进行尸检时采集的样本，这些年轻人 死于外因。这些样本来自多中心研究 由两项名为致病生物学决定因素的倡议资助 青年动脉粥样硬化(PDAY)与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) 大约715例PDAY-RFEHA患者的血清样本中的表型。这个 这项研究的终点将是衡量以下问题的程度和严重性 由病理学家在研究中确定的动脉粥样硬化。具体的 目的如下：1)测定载脂蛋白(A)亚型表型(分子 约715例PDAY-RFEHA患者的血清样本中的体重)；2)至 量化所有样品的每个波段的相对数量 可区分的apo(A)异构体条带；3)确定 载脂蛋白(A)分子量与术后病变范围和严重程度的关系 考虑到Lp(A)、脂蛋白胆固醇、吸烟、 种族、性别和年龄；以及4)确定种族和性别的影响 载脂蛋白(A)分子量与血管病变程度和严重程度的关系 损伤。这项研究的结果将被用来检验假设 载脂蛋白(A)大小表型的变化与 动脉粥样硬化病变。对人类健康的潜在长期益处 将是对高危表型的鉴定，以保证临床 干预。

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.