Differential Expression of Circulating Damage-Associated Molecular Patterns in Patients with Coronary Artery Ectasia
James N. Tsoporis,
Andreas S. Triantafyllis,
Andreas S. Kalogeropoulos,
Shehla Izhar,
Angelos G. Rigopoulos,
Loukianos S. Rallidis,
Eleftherios Sakadakis,
Ioannis K. Toumpoulis,
Vasileios Salpeas,
Howard Leong-Poi,
Thomas G. Parker,
Ioannis Rizos
Affiliations
James N. Tsoporis
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
Andreas S. Triantafyllis
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Andreas S. Kalogeropoulos
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Shehla Izhar
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
Angelos G. Rigopoulos
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Loukianos S. Rallidis
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Eleftherios Sakadakis
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Ioannis K. Toumpoulis
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Vasileios Salpeas
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
Howard Leong-Poi
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
Thomas G. Parker
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
Ioannis Rizos
Second Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
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.
