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再次手术切除的冠状动脉搭桥静脉移植物中载脂蛋白[a]和B的定量与定位

Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

作者信息

Cushing G L, Gaubatz J W, Nava M L, Burdick B J, Bocan T M, Guyton J R, Weilbaecher D, DeBakey M E, Lawrie G M, Morrisett J D

机构信息

Department of Medicine, Baylor College of Medicine, Methodist Hospital, Houston, Texas.

出版信息

Arteriosclerosis. 1989 Sep-Oct;9(5):593-603. doi: 10.1161/01.atv.9.5.593.

DOI:10.1161/01.atv.9.5.593
PMID:2789507
Abstract

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.

摘要

脂蛋白[a](Lp[a])是一种血浆浓度与心血管疾病高度相关的脂蛋白。其蛋白质部分载脂蛋白[a](apoLp[a])由两种大型多肽组成,即载脂蛋白[a](apo[a])和载脂蛋白B。在接受冠状动脉再次搭桥手术的患者群体中,研究了Lp[a]对大隐静脉主动脉冠状动脉旁路移植术中动脉粥样硬化的可能影响。将apoLp[a]的静脉移植物组织水平与移植物持续时间、大体和光学显微镜病理以及apoLp[a]的血浆水平进行了比较。确定了apo[a]和apo B在静脉移植物组织中的定位模式。此外,还测量了胆固醇、甘油三酯、载脂蛋白(apo)A-I、A-II和E的血浆水平。在一个由17名平均年龄为63岁的患者组成的代表性亚组中,切除了平均持续时间为112个月的移植物,平均总血浆胆固醇水平为221mg/dl,平均高密度脂蛋白胆固醇水平为31mg/dl,平均血浆甘油三酯水平为228mg/dl。在正常大隐静脉中,apoLp[a]的水平低于可测量范围(低于2ng/mg),apo B的水平非常低(3.3ng/mg)。在切除的移植物中,apoLp[a]的平均组织水平为32ng/mg,apo B的平均组织水平为70ng/mg,表明这些载脂蛋白从移植到动脉床时起就在静脉中净积累。在来自59个移植物(28名患者)的77个组织切片中测定了apoLp[a]/apo B比值,发现为0.313。该组织比值显著高于(p = 0.02)这些患者的血浆apoLp[a]/apo B比值,后者为0.132。免疫染色显示apo[a]和apo B在移植物的新内膜中共定位。在切除的移植物中观察到的最常见病理特征是内膜增生(43/52)、血栓形成(28/52)和动脉粥样硬化核心区域(21/52)。组织apo B水平与核心区域的丰度密切相关(r = 0.501),而组织apoLp[a]水平与该特征的相关性则不太好(r = 0.233)。尽管正常大隐静脉中几乎不存在apo[a]和apo B,但这些载脂蛋白(以及推测的脂蛋白Lp[a]和低密度脂蛋白)在旁路静脉移植物中积累。数据支持这些脂蛋白在静脉移植物动脉粥样硬化中起重要作用的观点。

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