Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events
Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events
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DOI：
10.1093/eurheartj/ehq387
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发表时间：
2011-07-01
影响因子：
39.3
通讯作者：
Pasterkamp, Gerard
中科院分区：
文献类型：
--
作者：
Peeters, Wouter;de Kleijn, Dominique P. V.;Pasterkamp, Gerard
目的：目前越来越需要通过转译研究来鉴定导致动脉粥样硬化斑块不稳定的分子靶点。与斑块易损性相关的局部分子斑块标记物可能具有预测价值，以识别患有心血管事件的风险增加的患者。动物研究表明脂肪细胞脂肪酸结合蛋白（FABP 4）与动脉粥样硬化的进展有关;然而，缺乏人动脉粥样硬化斑块中FABP 4表达的研究。我们研究了FABP 4的表达在颈动脉粥样硬化病变斑块成分和未来的心血管events.Methods和结果动脉粥样硬化斑块从561例接受颈动脉内膜切除术（CEA）。分析斑块中是否存在巨噬细胞、脂质核心、平滑肌细胞、胶原蛋白、钙化和斑块内出血。患者在CEA后随访3年。主要结局定义为血管性死亡、血管事件和手术或经皮血管介入治疗的复合终点。脂肪酸结合蛋白水平与不稳定斑块特征和症状性病变相关。FABP 4斑块水平增加的患者在随访期间达到主要结局的风险增加两倍[HR = 1.99，95%置信区间（95% CI）（1.30-3.04）]（P = 0.005）。FABP 4水平升高与主要结局相关，独立于一般心血管危险因素[HR 1.33，95%CI（1.08-1.65）]（P = 0.008）。结论动脉粥样硬化病变中的FABP 4水平与不稳定的斑块表型和随访期间心血管事件风险增加相关。除了对未来不良心血管事件进行风险分层外，本研究的结果支持探索FABP 4拮抗剂作为治疗动脉粥样硬化疾病进展的潜在药物干预的相关性。
Aims There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.Methods and results Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR 1.33, 95% CI (1.08-1.65)] (P = 0.008).Conclusion FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.