Cheng Jin M, Oemrawsingh Rohit M, Garcia-Garcia Hector M, Boersma Eric, van Geuns Robert-Jan, Serruys Patrick W, Kardys Isabella, Akkerhuis K Martijn
Erasmus MC, Department of Cardiology, Rotterdam, The Netherlands.
Erasmus MC, Department of Cardiology, Rotterdam, The Netherlands.
Atherosclerosis. 2016 May;248:117-22. doi: 10.1016/j.atherosclerosis.2016.03.010. Epub 2016 Mar 11.
Experimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels. This study aims to investigate the association between serum PCSK9 levels and the fraction and amount of necrotic core tissue in coronary atherosclerotic plaque, as assessed by intravascular ultrasound virtual histology (IVUS-VH) imaging.
Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina. PCSK9 concentrations were measured in serum samples that were drawn prior to coronary angiography. None of the patients received PCSK9 inhibitors.
After adjustment for established cardiac risk factors, statin use and serum LDL cholesterol, serum PCSK9 levels were linearly associated with the fraction of plaque consisting of necrotic core tissue (β = 1.24% increase per 100 μg/L increase in PCKS9, 95%CI 0.55-1.94, p = 0.001) and with the absolute volume of necrotic core tissue (β = 0.09, 95%CI 0.01-0.18, p = 0.033), but were not significantly associated with plaque burden (p = 0.11), plaque volume (p = 0.22) or the presence of IVUS-VH-derived thin-cap fibroatheroma lesions (p = 1.0).
Serum PCSK9 levels were linearly associated with the fraction and amount of necrotic core tissue in coronary atherosclerosis, independently of serum LDL cholesterol levels and statin use. Therefore, PCSK9 may be an interesting therapeutic target for the treatment of atherosclerotic disease beyond LDL cholesterol regulation.
实验研究表明，前蛋白转化酶枯草溶菌素9型（PCSK9）可能通过独立于低密度脂蛋白（LDL）胆固醇水平的机制直接促进导致动脉粥样硬化的炎症过程。本研究旨在通过血管内超声虚拟组织学（IVUS-VH）成像，探讨血清PCSK9水平与冠状动脉粥样硬化斑块中坏死核心组织的比例和数量之间的关联。
在2008年至2011年期间，对581例因急性冠状动脉综合征（ACS）或稳定型心绞痛接受冠状动脉造影的患者进行了非罪犯冠状动脉的IVUS-VH成像。在冠状动脉造影前采集的血清样本中测量PCSK9浓度。所有患者均未接受PCSK9抑制剂治疗。
在调整既定的心脏危险因素、他汀类药物使用和血清LDL胆固醇后，血清PCSK9水平与坏死核心组织构成的斑块比例呈线性相关（PCSK9每升高100μg/L，增加1.24%，95%CI 0.55-1.94，p = 0.001），与坏死核心组织的绝对体积呈线性相关（β = 0.09，95%CI 0.0-0.18，p = 0.033），但与斑块负荷（p = 0.11）、斑块体积（p = 0.22）或IVUS-VH衍生的薄帽纤维粥样瘤病变的存在（p = 1.0）无显著关联。
血清PCSK9水平与冠状动脉粥样硬化中坏死核心组织的比例和数量呈线性相关，独立于血清LDL胆固醇水平和他汀类药物使用。因此，PCSK9可能是除调节LDL胆固醇之外治疗动脉粥样硬化疾病的一个有意义的治疗靶点。
