The authors identified previously unreported associations of the ICAD, CD53, GRM1, and GSTmu proteins with atherosclerosis, diabetes, and nonfatal cardiovascular outcomes in a 3-year follow-up of 216 patients undergoing coronary angiography.
Key Findings
Methods
The study profiled serum proteins in patients undergoing coronary angiography to find proteins associated with atherosclerosis and its comorbidities.
The 3-year follow-up included 216 patients subjected to coronary angiography.
Coronary atherosclerosis was quantified with the Gensini score.
Peripheral atherosclerosis was assessed by B-mode ultrasound.
Serum proteins were profiled with an Explorer antibody microarray (Full Moon Biosystems, USA).
Methods
The top five proteins from the atherosclerotic microarray profile were validated by ELISA in the total cohort.
In-house or commercial ELISA kits were used for validation.
Validation covered the top five proteins from the atherosclerotic profile, including ICAD, CD53, GRM1, GSTmu, and IL-6.
Results
ICAD (DFF45/ICAD) was the only validated protein linked to both type 2 diabetes and the presence of coronary artery stenosis, regardless of stenosis severity.
The association with coronary stenosis held regardless of the severity of stenosis.
The abstract reports that only ICAD was linked to type 2 diabetes among the validated proteins, though IL-6 was also associated with diabetes.
Results
CD53 was associated with coronary stenosis.
The abstract reports this association without giving statistics.
Results
IL-6 was associated with diabetes.
The abstract reports this association without giving statistics.
Results
GSTmu (glutathione S-transferase Mu3) was associated with brachiocephalic stenosis ≥60% and with femoral and coronary arterial lesions.
The abstract reports the associations without giving statistics.
These span both peripheral (brachiocephalic, femoral) and coronary arterial sites.
Results
GRM1 (glutamate metabotropic receptor 1) was the only protein showing inverse associations with coronary stenosis and with cardiovascular outcomes.
Inverse association with coronary stenosis: r = -0.24, P = 0.025.
Inverse association with cardiovascular outcomes: r = -0.31, P = 0.007.
Results
GRM1 was inversely associated with femoral lesions ≥30%.
This extends the inverse association of GRM1 with atherosclerosis to peripheral (femoral) arteries.
The abstract gives no statistics for this association.
Conclusions
The authors conclude that ICAD, CD53, GRM1, and GSTmu have previously unreported associations with atherosclerosis, diabetes, and nonfatal cardiovascular outcomes.
The outcomes studied were nonfatal cardiovascular events over the 3-year follow-up.
The cohort comprised 216 patients.
What This Means
This study looked for proteins in the blood that are linked to hardening and narrowing of the arteries (atherosclerosis) and related conditions. Researchers followed 216 patients who had coronary angiography for three years. They screened blood proteins with an antibody microarray, then confirmed the top candidates with standard lab tests (ELISA).
Several proteins showed links to artery disease. ICAD was linked to type 2 diabetes and to narrowed coronary arteries. CD53 was also linked to coronary narrowing. GSTmu was linked to narrowing in neck-area (brachiocephalic), leg (femoral), and coronary arteries. IL-6 was linked to diabetes. GRM1 behaved differently: higher levels were associated with less coronary narrowing, fewer non-fatal cardiovascular events (r = -0.24 and -0.31), and fewer femoral artery lesions.
This research suggests these proteins may be candidate markers or contributors in atherosclerosis and diabetes, and that GRM1 might be linked to a protective pattern. The associations were previously unreported, and the study is observational with a fairly small group, so it cannot show that these proteins cause or predict disease. Larger studies would be needed to confirm the findings.
Gumanova N, Mols A, Levshina A, Khadorich M, Luboyatnikova E, Shanoyan A, et al.. (2026). Novel Relationships between the ICAD, CD53, GRM1, and GSTmu Protein Levels and Atherosclerosis and Cardiovascular Outcomes.. Journal of proteome research. https://doi.org/10.1021/acs.jproteome.5c00843