Abstract:
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.
摘要:
冠状动脉扩张症(CAE)定义为直径超过相邻正常动脉段直径>1.5倍的冠状动脉异常扩张。CAE是冠状动脉的病理实体,其特征是冠状动脉粥样硬化的变体。CAE经常与冠状动脉疾病(CAD)共存。虽然炎症似乎参与其中,CAE的病理生理学尚不清楚.损伤相关分子模式(DAMPs),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。炎症剂可产生DAMP,而DAMP可产生促炎状态。在一项前瞻性横断面研究中,我们招募了29例CAE和非阻塞性CAD患者,19例梗阻性CAD无CAE,和14名与CAE患者年龄和性别匹配的正常(对照)冠状动脉对照受试者,探讨血浆DAMPs的差异表达。CAE和非阻塞性CAD患者的DAMPS100B血浆水平升高,与CAD和对照相比,S100A12、HMGB1和HSP70、DAMPs受体TLR4和miR328a-3p。mir328a-3p的血浆水平靶向晚期糖基化终产物(sRAGE)的DAMPs受体的保护性可溶形式,与对照组相比,CAE和CAD中的抗氧化剂DJ-1均降低。在体外人脐静脉内皮细胞模型中,S100B的循环水平,HMGB1、HSP70以及CAE患者血浆诱导的炎症反应。DAMPsS100B的差异表达,HSP70,HMGB1及其受体TLR4和sRAGE在CAE与CAD中的作用使它们成为有吸引力的新型生物标志物作为治疗靶标和治疗剂。