Novel Relationships between the ICAD, CD53, GRM1, and GSTmu Protein Levels and Atherosclerosis and Cardiovascular Outcomes

Abstract

The aim of the present study was to identify serum proteins associated with atherosclerosis and its comorbidities. The 3-year follow-up included 216 patients subjected to coronary angiography. Gensini score was used to quantify coronary atherosclerosis, and peripheral atherosclerosis was assessed by B-mode ultrasound. Serum proteins were profiled using an Explorer antibody microarray (Full Moon Biosystems, USA). In-house ELISA or commercial ELISA kits were used to validate the microarray data in the total cohort for the top five proteins from the atherosclerotic profile. Only ICAD (DNA fragmentation factor subunit, DFF45/ICAD) was linked to type 2 diabetes and the presence of coronary artery stenosis regardless of the severity of stenosis. CD53 was also associated with coronary stenosis. IL-6 was associated with diabetes, and GSTmu (glutathione S-transferase Mu3) was associated with brachiocephalic stenosis ≥ 60% and with femoral and coronary arterial lesions. Only GRM1 (glutamate metabotropic receptor 1) showed inverse associations with coronary stenosis and cardiovascular outcomes (r = −0.24 and P = 0.025 and r = −0.31 and P = 0.007, respectively). Moreover, GRM1 was inversely associated with femoral lesions ≥ 30%. Thus, we identified previously unreported associations of the ICAD, CD53, GRM1, and GSTmu proteins with atherosclerosis, diabetes, and nonfatal cardiovascular outcomes.