Inova Heart and Vascular Institute, Falls Church, Virginia.
Program in Nutritional Metabolism, MGH and Harvard Medical School, Boston.
AIDS. 2018 Apr 24;32(7):867-876. doi: 10.1097/QAD.0000000000001762.
HIV patients have increased atherosclerotic coronary vascular disease (ASCVD), thought to be mediated through inflammatory mechanisms. We hypothesized that among asymptomatic HIV-infected patients with subclinical coronary plaque, statin therapy would modulate unique inflammatory and cardiovascular proteins in relation to change in subclinical coronary plaque volume. We tested this hypothesis using a novel proteomics approach.
Forty HIV-infected participants were randomized to atorvastatin (40 mg/day) versus placebo, and underwent computed tomography coronary angiography to quantify plaque volume at baseline and 1 year.
We used Olink Cardiovascular III and Cardiometabolic panels based on dual antibody epitope recognition with linked DNA amplification to compare change over time in 184 proteins in treatment versus placebo and in relation to change in coronary plaque volume.
Six proteins (TFPI, CCL24, NT-Pro BNP, MBL2, LTBR, PCOLCE) changed significantly in the atorvastatin versus placebo group, many in innate immune and other novel inflammatory pathways. Twenty-six proteins changed significantly in relationship to total coronary plaque volume over 1 year. Notably, many of these proteins changed only weakly in relationship to change in low-density lipoprotein (LDL). Overlapping these two broad discovery approaches, proteins involved in myocardial fibrosis/collagen formation and monocyte chemoattraction changed with statin treatment, in relationship to plaque volume, but not LDL.
This proof-of-concept study employing a proteomic discovery platform offers insight into statin effects on novel immune pathways relevant to ASCVD progression in HIV. Novel biomarker discovery may enhance precision medicine strategies to estimate the efficacy of targeted therapies to reduce ASCVD progression and events in HIV.
HIV 患者的动脉粥样硬化性冠状动脉血管疾病（ASCVD）发病率增加，据认为这是通过炎症机制介导的。我们假设，在无症状的、有亚临床冠状动脉斑块的 HIV 感染者中，他汀类药物治疗将调节与亚临床冠状动脉斑块体积变化相关的独特炎症和心血管蛋白。我们使用一种新的蛋白质组学方法来检验这一假设。
40 名 HIV 感染者被随机分配至阿托伐他汀（40mg/天）或安慰剂组，并接受计算机断层冠状动脉造影术，以在基线和 1 年时量化斑块体积。
我们使用 Olink 心血管 III 和心脏代谢面板，基于双抗体表位识别与 DNA 连接扩增，比较治疗与安慰剂组以及与冠状动脉斑块体积变化相关的 184 种蛋白质随时间的变化。
阿托伐他汀与安慰剂组相比，有 6 种蛋白质（TFPI、CCL24、NT-Pro BNP、MBL2、LTBR、PCOLCE）发生了显著变化，其中许多涉及固有免疫和其他新的炎症途径。在 1 年内，有 26 种蛋白质与总冠状动脉斑块体积显著相关。值得注意的是，其中许多蛋白质与低密度脂蛋白（LDL）的变化仅弱相关。通过重叠这两种广泛的发现方法，与斑块体积相关的、涉及心肌纤维化/胶原形成和单核细胞趋化作用的蛋白质发生了变化，但与 LDL 无关。
这项采用蛋白质组学发现平台的概念验证研究提供了他汀类药物对 HIV 相关 ASCVD 进展的新型免疫途径的作用的见解。新的生物标志物发现可能增强精准医学策略，以评估靶向治疗降低 HIV 患者 ASCVD 进展和事件的疗效。
