Abstract 12556: The Matrikine Proline-Glycine-Proline is a Novel Biomarker of Coronary Artery Disease Amongst Patients With Chronic Obstructive Pulmonary Disease

Abstract

Introduction: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of coronary artery disease (CAD). Proline-glycine-proline (PGP) is an extracellular matrix-derived chemokine ( matrikine ) that is increased in COPD and known to promote neutrophil chemotaxis, endothelial dysfunction, and vascular inflammation through activation of the CXC Chemokine Receptor 2 (CXCR2). Despite these observations, no study has examined PGP as a marker of CAD within COPD patients. Hypothesis: We hypothesized that circulating PGP is associated with comorbid CAD amongst COPD patients. Methods: Current and former smokers with COPD enrolled in the UAB P rospective R epository for coupling EVE nts to N ovel pa T hways in COPD (PREVENT COPD) cohort underwent phlebotomy and spirometry. Cardiovascular diagnoses were adjudicated by two physician reviewers with access to medical records. CAD was defined as a composite of prior myocardial infarction, coronary revascularization, or by physician diagnosis of CAD. Plasma PGP was measured using a solid-phase extraction method coupled with tandem mass spectrometry. Other known CXCR2 ligands (e.g. GRO alpha, IL-8) were measured by multiplex protein assay. SPSSv27 was used for logistic regression models to measure associations between plasma biomarkers and the presence of CAD. Results: The 104 participants were 60±9 years old, 50% male, and 50% Black race. CAD was prevalent in 21 (21%) of the cohort. Plasma PGP was detectable for all participants (0.05 - 15.1 ng/mL). Participants with CAD had higher PGP concentrations compared to participants without CAD (1.26 vs. 0.52 ng/mL, p=0.042). Similarly, PGP was increased among participants with prior coronary revascularization (p<0.01). Associations between plasma PGP and CAD remained significant after adjustment for FEV1 % predicted and smoking status (OR 1.62, 95%CI 1.02-2.56). Concentrations of other CXCR2 ligands were low and not associated with CAD. Conclusions: Our results highlight PGP as a potentially novel biomarker of CAD among individuals with COPD. Future studies are needed to assess whether plasma PGP is predictive of CAD outcomes in COPD, as well as determine the significance of endothelial CXCR2 activation on the development of atherosclerosis.