Lipoprotein(a) and inflammation in human coronary atheroma: Association with the severity of clinical presentation
Lipoprotein(a) and inflammation in human coronary atheroma: Association with the severity of clinical presentation
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DOI：
10.1016/s0735-1097(98)00469-0
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发表时间：
1998-12-01
影响因子：
24
通讯作者：
Fallon, JT
中科院分区：
文献类型：
--
作者：
Dangas, G;Mehran, R;Fallon, JT
目标。本研究的目的是探讨脂蛋白(A)[Lp(A)]和炎性浸润物在人冠状动脉粥样硬化斑块中的作用及其与临床症状的相关性。脂蛋白(A)是一种致动脉粥样硬化和血栓形成的脂蛋白，在急性冠脉综合征的发病机制中起重要作用。在体外，脂蛋白(A)可诱导单核细胞趋化和平滑肌细胞活化。巨噬细胞浸润被认为是斑块破裂的机制之一。本研究以动脉粥样硬化切除标本为研究对象，探讨脂蛋白(A)在动脉粥样硬化形成过程不同阶段的体内作用及其与巨噬细胞浸润的关系。我们对72例稳定性心绞痛或不稳定型心绞痛患者的冠状动脉斑块进行了检测。标本用Lp(A)、巨噬细胞(KP-1)和平滑肌细胞(α-肌动蛋白)特异性抗体染色，形态计量学分析定量这三种抗原所占据的斑块面积及其共存结果。所有标本均有Lp(A)染色，平均面积为58.2%。90%的巨噬细胞区与Lp(A)阳性区共存，31.3%的平滑肌细胞区与Lp(A)阳性区共存。不稳定型心绞痛患者(n=46)的Lp(A)斑块平均面积大于稳定型心绞痛患者(n=26)，分别为64.4%和47.7%(P=0.004)。不稳定性心绞痛伴静息性疼痛患者(n=28)的Lp(A)平均面积大于不稳定型心绞痛伴劳力性心绞痛患者(n=18)：71.1%对52.4%(p<；0.001)，不稳定劳力性心绞痛患者平均KP-1面积为31.2%，稳定性心绞痛组为18.3%(P=0.001)；斑块Kp-1与Lp(A)面积相关性最强的是不稳定静息型心绞痛(r=0.001.88，p<；0.0 1)，新月劳力型心绞痛的α-肌动蛋白与Lp(A)面积相关性最强(r=0.62，p<；0.0 1)。脂蛋白(A)在人类冠状动脉粥样硬化中普遍存在，与稳定型相比，不稳定型患者的罪犯病变组织中检测到更多的脂蛋白(A)，并与斑块巨噬细胞显著共存。斑块α-肌动蛋白与Lp(A)面积的相关性提示Lp(A)在斑块生长中起作用。(J Am Coll心脏ol 1998；32：2035-42)(C)1998由美国心脏病学会出版。
Objectives. The purpose of this study was the investigation of the in vivo role of lipoprotein(a) [Lp(a)] and inflammatory infiltrates in the human coronary atherosclerotic plaque and their correlation with the clinical syndrome of presentation.Background. Lipoprotein(a) is an atherogenic and thrombogenic lipoprotein, and has been implicated in the pathogenesis of acute coronary syndromes, Lipoprotein(a) induces monocyte chemoattraction and smooth muscle cell activation in vitro. Macrophage infiltration is considered one of the mechanisms of plaque rupture.Methods. This study of atherectomy specimens investigated the in vivo role of Lp(a) at different stages of the atherogenic process, and its relationship with macrophage infiltration. We examined coronary atheroma removed from 72 patients with stable or unstable angina. Specimens were stained with antibodies specific for Lp(a), macrophages (KP-1), and smooth muscle cells (alpha-actin), Morphometric analysis was used to quantify the plaque areas occupied by each of the three antigens, and their colocalization,Results. All specimens had localized Lp(a) staining; the mean fractional area was 58.2%. Ninety percent of the macrophage areas colocalized with Lp(a) positive areas,whereas 31.3% of the smooth muscle cell areas colocalized with Lp(a) positive areas. Patients with unstable angina (n = 46) had specimens with larger mean plaque Lp(a) areas than specimens from stable angina patients (n = 26): 64.4% versus 47.7% (p = 0.004). Unstable angina patients with rest pain (n = 28) had greater mean plaque Lp(a) area than unstable angina patients with crescendo exertional pain (n = 18): 71.1% versus 52.4% (p < 0.001), Mean KP-1 area was 31.2% in unstable rest angina versus 18.3% in stable angina (p = 0.05); alpha actin area was greater in stable (48.5%) and crescendo exertional angina (48.8%) than in rest angina (30.4%). The strongest correlation between plaque KP-1 and Lp(a) area was in unstable rest angina (r = 0.88, p < 0.001), and between alpha-actin and Lp(a) areas in the crescendo exertional angina (r = 0.62, p < 0.01).Conclusions. Lipoprotein(a) is ubiquitous in human coronary atheroma, It is detected in larger amounts in tissue from culprit lesions in patients with unstable compared to stable syndromes, and has significant colocalization with plaque macrophages. A correlation of plaque alpha-actin and Lp(a) area suggests a role of Lp(a) in plaque growth. (J Am Coll Cardiol 1998;32:2035-42) (C) 1998 by the American College of Cardiology.