Department of Geriatric Medicine, Qilu Hospital of Shandong University; Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China.
Population Health Division, San Francisco Department of Public Health, San Francisco, CA, United States.
Int J Cardiol. 2022 Mar 1;350:9-15. doi: 10.1016/j.ijcard.2022.01.014. Epub 2022 Jan 7.
Low-density lipoprotein receptor (LDLR) is the primary pathway for removal of cholesterol from the circulation, pro-protein convertase subtilisin-like kexin type 9 (PCSK9) is a secreted protease that binds to and promotes degradation of the LDLR protein. The goal of this case-control study was to investigate the role of soluble LDLR (sLDLR) and PCSK9 in coronary artery disease (CAD) and investigate the relationship between these two indices and CAD.
In a sample of 144 Chinese patients recruited between January 2018 and August 2018, 81 cases with mild and severe stenosis characterized by coronary angiograph (CAG) and 63 healthy controls were selected using the propensity score matching (PSM) based on demographics and medical history. sLDLR and PCSK9 concentrations were determined using enzyme-linked immunosorbent assay (ELISA), Immuno-precipitation (IP) and western blotting. Multivariable logistic models were used to assess the associations between the degree of coronary artery stenosis and the biomarkers of interest.
Higher PCSK9 was found to be a significant predictor of coronary artery stenosis when comparing cases who had severe stenosis vs. controls (OR=1.016, 95%CI: 1.009, 1.024), and cases who had mild stenosis vs. controls (OR=1.009, 95%CI: 1.003, 1.015). sLDLR was positively corrected with PCSK9, which confounded the association between CAD and PCSK9. Compared to patients with mild-stenosis, patients with severe-stenosis also showed a higher level of PCSK9 (OR=1.007, 95%CI: 1.001, 1.013).
These findings suggest that elevated PSCK9 may contribute to the odds of developing CAD, with a higher degree of coronary artery stenosis.
低密度脂蛋白受体（LDLR）是循环中胆固醇清除的主要途径，前蛋白转化酶枯草溶菌素 9（PCSK9）是一种分泌型蛋白酶，可与 LDLR 蛋白结合并促进其降解。本病例对照研究旨在探讨可溶性 LDLR（sLDLR）和 PCSK9 在冠状动脉疾病（CAD）中的作用，并研究这两个指标与 CAD 的关系。
在 2018 年 1 月至 2018 年 8 月期间招募的 144 名中国患者中，通过基于人口统计学和病史的倾向评分匹配（PSM）选择 81 例具有冠状动脉造影（CAG）轻度和重度狭窄的病例和 63 例健康对照者。使用酶联免疫吸附试验（ELISA）、免疫沉淀（IP）和 Western blot 测定 sLDLR 和 PCSK9 浓度。多变量逻辑模型用于评估冠状动脉狭窄程度与感兴趣的生物标志物之间的关系。
与严重狭窄组相比，对照组（OR=1.016，95%CI：1.009，1.024）和轻度狭窄组（OR=1.009，95%CI：1.003，1.015）中，PCSK9 升高是冠状动脉狭窄的显著预测因子。sLDLR 与 PCSK9 呈正相关，这混淆了 CAD 与 PCSK9 之间的关系。与轻度狭窄组患者相比，重度狭窄组患者的 PCSK9 水平也更高（OR=1.007，95%CI：1.001，1.013）。
这些发现表明，PCSK9 升高可能导致 CAD 的发病几率增加，且冠状动脉狭窄程度越高。
