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Free Thiol β2-GPI (β-2-Glycoprotein-I) Provides a Link Between Inflammation and Oxidative Stress in Atherosclerotic
James C Weaver1,2, Inaam Ullah1,3, Miao Qi1,4
1University of NSW, Sydney, Australia (J.C.W., I.U., M.Q., B.G., K.A.R., S.A.K.).
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.
Insights
Higher levels of free thiol beta-2-glycoprotein I (β2-GPI) predict the presence and severity of stable coronary artery disease. This redox form was a stronger predictor than high-sensitivity C-reactive protein.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Oxidative Stress Research
Background:
- Atherosclerotic coronary artery disease is an inflammatory condition influenced by oxidative stress.
- Beta-2-glycoprotein I (β2-GPI) is a plasma protein with distinct free thiol and oxidized redox forms.
- The role of β2-GPI redox states in coronary artery disease pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the association between the post-translational redox forms of β2-GPI and atherosclerotic coronary artery disease.
- To determine if free thiol β2-GPI predicts the presence and extent of coronary artery disease in stable patients.
- To compare the predictive value of free thiol β2-GPI against hs-CRP in stable coronary artery disease.
Main Methods:
- Prospective recruitment of stable patients undergoing coronary angiography and acute coronary syndrome patients post-myocardial infarction.
- Quantification of total and free thiol β2-GPI levels in serum and plasma.
- Assessment of coronary artery disease extent using Syntax and Gensini scores.
Main Results:
- Total β2-GPI levels did not correlate with stable coronary artery disease.
- Elevated free thiol β2-GPI levels were significantly associated with the presence and extent of stable coronary artery disease.
- Free thiol β2-GPI demonstrated superior predictive capability for stable coronary artery disease compared to hs-CRP.
- Conversely, lower free thiol β2-GPI levels were observed in patients with ST-segment-elevation myocardial infarction.
Conclusions:
- Free thiol β2-GPI serves as a significant predictor of coronary artery disease presence and severity in stable patients.
- The predictive power of free thiol β2-GPI surpasses that of hs-CRP for stable coronary artery disease.
- The paradoxical finding of lower free thiol β2-GPI in acute myocardial infarction warrants further investigation.
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Coronary Artery Disease I: Introduction
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Atherosclerosis II: Clinical Manifestations and Diagnostic Tests

