Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study

作者：David M. Leistner, Nicolle Kränkel, Denitsa Meteva, Youssef Salah Abdelwahed, Claudio Seppelt, Barbara Elisabeth Stähli, Himanshu Rai, Carsten Skurk, Alexander Lauten, Hans‐Christian Mochmann, Georg Fröhlich, Ursula Rauch‐Kröhnert, Eduardo Flores, Matthias Riedel, Lara Sieronski, Sylvia Kia, Elisabeth Tamara Strässler, Arash Haghikia, Fabian Dirks, Julia Steiner, Dominik N. Mueller, Hans‐Dieter Volk, Jens Klotsche, Michael Joner, Peter Libby, Ulf Landmesser · 发表于：European Heart Journal · 年份：2020 · DOI：10.1093/eurheartj/ehaa703 · 被引用次数：108 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Coronary Interventions and Diagnostics、Cardiac and Coronary Surgery Techniques

AIMS: Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. METHODS AND RESULTS: The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significan...