Lundberg G A, Kellin A, Samnegård A, Lundman P, Tornvall P, Dimmeler S, Zeiher A M, Hamsten A, Hansson G K, Eriksson P
Department of Caring Sciences, Biomedicine, Orebro University, Orebro, Sweden.
J Intern Med. 2005 May;257(5):415-22. doi: 10.1111/j.1365-2796.2005.01469.x.
Enhanced expression of CXCL16 has been demonstrated in atherosclerotic plaques and several properties have been attributed to CXCL16 that could influence the atherosclerotic process. CXCL16 exists in transmembrane and soluble forms. The transmembrane form acts as a scavenger receptor for oxidised LDL whereas the soluble form acts a chemoattractant for mainly CD8+ T cells. In addition, the soluble form of CXCL16 influences human aortic smooth muscle cell proliferation in vitro. In the present work, a human molecular genetic approach employing a common polymorphism within exon 4 of CXCL16 (181 Ala>Val) was used to investigate whether CXCL16 may be involved in the development of coronary artery disease. The polymorphism is located within the spacer region between the chemokine and transmembrane region and potentially influences an Ala/Val cleavage site, a site commonly used for the release of chemokines by tumour necrosis factor-alpha converting enzyme.
We first genotyped 387 unselected survivors of a first myocardial infarction aged <60 years and 387 sex- and age-matched controls. A subset of patients (n = 236) was evaluated by quantitative coronary angiography. Secondly, a cohort of 468 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with stent implantation was genotyped.
No significant difference in allele frequency between patient and controls of the 181 A>V polymorphism was detected. However, the V-allele was associated with increased severity of coronary stenoses. Secondly, the V-allele was associated with smaller minimal luminal diameter in the coronary segment subjected to intervention in a second cohort of patients undergoing PTCA with stent implantation.
The present work provides evidence that CXCL16 is involved in processes leading to enhanced stenosis in atherosclerotic coronary arteries.
CXCL16在动脉粥样硬化斑块中的表达增强，且CXCL16的多种特性被认为可影响动脉粥样硬化进程。CXCL16以跨膜和可溶性两种形式存在。跨膜形式作为氧化型低密度脂蛋白的清道夫受体，而可溶性形式主要作为CD8 + T细胞的趋化因子。此外，CXCL16的可溶性形式在体外影响人主动脉平滑肌细胞的增殖。在本研究中，采用一种人类分子遗传学方法，利用CXCL16第4外显子内的一个常见多态性位点（181 Ala>Val），来研究CXCL16是否可能参与冠状动脉疾病的发生发展。该多态性位于趋化因子和跨膜区域之间的间隔区，可能影响丙氨酸/缬氨酸切割位点，这是肿瘤坏死因子-α转换酶释放趋化因子常用的一个位点。
我们首先对387例年龄小于60岁的首次心肌梗死未筛选幸存者和387例性别及年龄匹配的对照者进行基因分型。一部分患者（n = 236）通过定量冠状动脉造影进行评估。其次，对468例行经皮冠状动脉腔内血管成形术（PTCA）并植入支架的患者进行基因分型。
在181 A>V多态性的等位基因频率上，患者与对照者之间未检测到显著差异。然而，V等位基因与冠状动脉狭窄的严重程度增加相关。其次，在第二组行PTCA并植入支架的患者中，V等位基因与干预冠状动脉节段的最小管腔直径较小相关。
本研究提供了证据，表明CXCL16参与了导致动脉粥样硬化性冠状动脉狭窄加重的过程。
