Free Thiol β2-GPI (β-2-Glycoprotein-I) Provides a Link Between Inflammation and Oxidative Stress in Atherosclerotic Coronary Artery Disease

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 40; no. 11; pp. 2794 - 2804
• Main Authors: Weaver, James C, Ullah, Inaam, Qi, Miao, Giannakopoulos, Bill, Rye, Kerry Anne, Kockx, Maaike, Kritharides, Leonard, Krilis, Steven A
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.11.2020
• Subjects: Acute Coronary Syndrome - blood; Acute Coronary Syndrome - diagnostic imaging; Aged; beta 2-Glycoprotein I - blood; Biomarkers - blood; C-Reactive Protein - analysis; Coronary Angiography; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Female; Heart Disease Risk Factors; Humans; Inflammation - blood; Inflammation - diagnosis; Inflammation Mediators - blood; Lipids - blood; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Predictive Value of Tests; Prospective Studies; ST Elevation Myocardial Infarction - blood; ST Elevation Myocardial Infarction - diagnostic imaging; coronary artery disease; coronary angiography; metabolome; cysteine; proteome
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.120.315156

OBJECTIVE:Atherosclerotic coronary artery disease is well recognised as an inflammatory disorder that is also influenced by oxidative stress. β2-GPI (β-2-glycoprotein-I) is a circulating plasma protein that undergoes post-translational modification and exists in free thiol as well as oxidized forms. The aim of this study was to assess the association between these 2 post-translational redox forms of β2-GPI and atherosclerotic coronary artery disease. APPROACH AND RESULTS:Stable patients presenting for elective coronary angiography or CT coronary angiography were prospectively recruited. A separate group of patients after reperfused ST-segment–elevation myocardial infarction formed an acute coronary syndrome subgroup. All patients had collection of fasting serum and plasma for quantification of total and free thiol β2-GPI. Coronary artery disease extent was quantified by the Syntax and Gensini scores. A total of 552 patients with stable disease and 44 with acute coronary syndrome were recruited. While total β2-GPI was not associated with stable coronary artery disease, a higher free thiol β2-GPI was associated with its presence and extent. This finding remained significant after correcting for confounding variables, and free thiol β2-GPI was a better predictor of stable coronary artery disease than hs-CRP (high-sensitivity C-reactive protein). Paradoxically, there were lower levels of free thiol β2-GPI after ST-segment–elevation myocardial infarction. CONCLUSIONS:Free thiol β2-GPI is a predictor of coronary artery disease presence and extent in stable patients. Free thiol β2-GPI was a better predictor than high-sensitivity C-reactive protein.