Abstract 12511: Differential Regulation of Circulating Damage-Associated Molecular Patterns in Patients With Coronary Artery Ectasia

Abstract

Introduction: Coronary artery ectasia (CAE) defined as localized or diffuse non-obstructive coronary lesions is a rare but well-recognized pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE commonly coexists with coronary artery disease (CAD). Although inflammation appears to be involved, the pathophysiology behind CAE remains unclear. Danger-associated molecular patterns (DAMPs) are altered metabolism products of necrotic or stressed cells, which are deemed as alarm signals by the innate immune system. Inflammatory agents are DAMP generators and DAMPs create a pro-inflammatory state. Hypothesis: We aimed to investigate the different patterns of serum DAMPs in patients with CAE, obstructive CAD and normal coronary arteries and the prognostic role of these in the pathogenesis of CAE. Methods: In this prospective cross-sectional study, 28 patients with CAE and nonobstructive CAD were enrolled in the study, 19 patients with obstructive CAD but without CAE, and 18 control subjects with normal coronary arteries that have been matched with the CAE patients for age and sex were also enrolled in our study population. Venous blood samples of the participants were collected for serum DAMP evaluation. Results: Patients with CAE and non-obstructive CAD had increased (30-35%) serum levels of the DAMPs, the receptor for advanced glycation end products (RAGE) ligand S100B and the toll-like receptor 4 ligand heat shock protein (HSP)70 compared to control subjects and patients with CAD. Additionally, CAE and non-obstructive CAD patients had decreased (30-40%) serum levels of potential DAMPs, the antioxidant DJ-1 and soluble (s)RAGE, a decoy molecule that bind excess RAGE ligands, compared to control subjects and CAD patients. Positive correlations were observed between S100B and HSP70 (p=00564), and DJ-1 and sRAGE (p=0.00461). All evaluated serum DAMPs were not different in CAD patients compared to control subjects. Conclusion: The differential regulation of the DAMPs S100B, HSP70, DJ-1 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.