Tsoporis James N, Triantafyllis Andreas S, Kalogeropoulos Andreas S, Izhar Shehla, Rigopoulos Angelos G, Rallidis Loukianos S, Sakadakis Eleftherios, Toumpoulis Ioannis K, Salpeas Vasileios, Leong-Poi Howard, Parker Thomas G, Rizos Ioannis
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond St., Toronto, ON M5B 1W8, Canada.
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece.
Biomolecules. 2023 Dec 21;14(1):10. doi: 10.3390/biom14010010.
Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system. Inflammatory agents can generate DAMPs and DAMPs can create a pro-inflammatory state. In a prospective cross-sectional study, we enrolled 29 patients with CAE and non-obstructive CAD, 19 patients with obstructive CAD without CAE, and 14 control subjects with normal (control) coronary arteries age- and sex-matched with the CAE patients, to investigate the differential expression of plasma DAMPs. Patients with CAE and non-obstructive CAD had increased plasma levels of the DAMPs S100B, S100A12, HMGB1, and HSP70, the DAMPs receptor TLR4, and miR328a-3p compared to CAD and controls. Plasma levels of the mir328a-3p target the protective soluble form of the DAMPs receptor for advanced glycation end products (sRAGE), and the antioxidant DJ-1 was decreased in both CAE and CAD compared to controls. In an in vitro human umbilical vein endothelial cells model, circulating levels of S100B, HMGB1, HSP70 as well as CAE patient plasma induced inflammatory responses. The differential expression of the DAMPs S100B, HSP70, HMGB1, and their receptors TLR4 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.
冠状动脉扩张（CAE）被定义为冠状动脉的异常扩张，其直径超过相邻正常动脉节段直径的1.5倍以上。CAE是冠状动脉的一种病理实体，被认为是冠状动脉粥样硬化的一种变体。CAE常与冠状动脉疾病（CAD）共存。虽然炎症似乎与之相关，但CAE的病理生理学仍不清楚。损伤相关分子模式（DAMPs）被定义为从应激或受损组织释放的内源性分子，被先天免疫系统视为警报信号。炎症因子可产生DAMPs，而DAMPs可引发促炎状态。在一项前瞻性横断面研究中，我们纳入了29例患有CAE和非阻塞性CAD的患者、19例无CAE的阻塞性CAD患者以及14例年龄和性别与CAE患者匹配的冠状动脉正常（对照）受试者，以研究血浆DAMPs的差异表达。与CAD患者和对照组相比，患有CAE和非阻塞性CAD的患者血浆中DAMPs S100B、S100A12、HMGB1和HSP70、DAMPs受体TLR4以及miR328a - 3p水平升高。miR328a - 3p的血浆水平靶向晚期糖基化终产物（sRAGE）的保护性可溶性DAMPs受体形式，与对照组相比，CAE和CAD患者的抗氧化剂DJ - 1均降低。在体外人脐静脉内皮细胞模型中，S100B、HMGB1、HSP70的循环水平以及CAE患者血浆均可诱导炎症反应。与CAD相比，CAE中DAMPs S100B、HSP70、HMGB1及其受体TLR4和sRAGE的差异表达使其成为作为治疗靶点和治疗方法的有吸引力的新型生物标志物。
