DOI: 10.3390/ijms27167246 ISSN: 1422-0067

Levels of ER Stress Markers GRP78, CHOP, and PERK in Cardiovascular Diseases

Tülay Oskay, Alten Oskay, Mert Özen, Isık Tekin, Fırat Okta, Abdo A. Elfiky, Murat Seyit, Atakan Yılmaz, Hakan Akça, Ibrahim Türkçüer, Gergana Lengerova, Martina Bozhkova, Steliyan Petrov, Aylin Köseler

Cardiovascular diseases remain the leading cause of mortality worldwide, and endoplasmic reticulum (ER) stress has emerged as an important molecular mechanism underlying myocardial injury and heart failure. This study investigated the expression of the ER stress-related genes GRP78, PERK, and CHOP in peripheral whole blood obtained from patients with acute cardiovascular diseases. A total of 300 participants were enrolled, including 200 patients with ST-segment elevation myocardial infarction (STEMI, n = 55), non-ST-segment elevation myocardial infarction (NSTEMI, n = 88), decompensated heart failure (DHF, n = 40), or unstable angina pectoris (USAP, n = 17), and 100 healthy controls. Relative mRNA expression levels were quantified using quantitative real-time PCR. Intergroup comparisons were performed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Bonferroni adjustment. Significant differences in GRP78, PERK, and CHOP expression were observed among the study groups (all p < 0.001). GRP78 and PERK expression levels were highest in the STEMI and DHF groups, whereas CHOP expression was highest in the STEMI group. Significant positive correlations were identified between troponin and CHOP (r = 0.48), GRP78 (r = 0.42), and PERK (r = 0.39) (all p < 0.001), while weaker but significant associations were observed between inflammatory markers (CRP and NLR) and ER stress-related gene expression. Exploratory receiver operating characteristic (ROC) analysis showed that CHOP demonstrated the highest discriminatory performance for distinguishing patients with acute cardiovascular disease from healthy controls. These findings indicate that peripheral whole-blood ER stress-related gene expression is associated with acute cardiovascular disease and correlates with established biomarkers of myocardial injury and inflammation. Further prospective studies are required to determine the clinical significance of these findings.

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