Peripheral whole-blood expression of ER stress-related genes GRP78, PERK, and CHOP is significantly elevated in acute cardiovascular diseases and correlates with established biomarkers of myocardial injury and inflammation, with CHOP demonstrating the highest discriminatory performance for distinguishing patients with acute cardiovascular disease from healthy controls.
Key Findings
Results
Significant differences in GRP78, PERK, and CHOP mRNA expression were observed among all study groups.
All three ER stress markers showed statistically significant intergroup differences (all p < 0.001)
Comparisons were performed using the Kruskal-Wallis test followed by Dunn's post hoc test with Bonferroni adjustment
A total of 300 participants were enrolled: 200 patients with acute cardiovascular diseases and 100 healthy controls
Patient groups included STEMI (n = 55), NSTEMI (n = 88), DHF (n = 40), and USAP (n = 17)
mRNA expression was quantified from peripheral whole blood using quantitative real-time PCR
Results
GRP78 and PERK expression levels were highest in the STEMI and DHF groups.
Among the four cardiovascular disease groups, STEMI and DHF patients showed the greatest upregulation of GRP78 and PERK
STEMI group comprised 55 patients and DHF group comprised 40 patients
Expression was measured in peripheral whole blood rather than cardiac tissue
These findings suggest particularly pronounced ER stress activation in the context of acute myocardial infarction and decompensated heart failure
Results
CHOP expression was highest in the STEMI group among all cardiovascular disease groups.
CHOP, a transcription factor associated with ER stress-induced apoptosis, showed peak expression in STEMI patients (n = 55)
CHOP expression differences across groups were statistically significant (p < 0.001)
CHOP also demonstrated the highest discriminatory performance in exploratory ROC analysis for distinguishing patients with acute cardiovascular disease from healthy controls
STEMI represents the most severe form of acute coronary syndrome included in the study
Results
Significant positive correlations were identified between troponin levels and all three ER stress markers.
Troponin correlated with CHOP (r = 0.48, p < 0.001)
Troponin correlated with GRP78 (r = 0.42, p < 0.001)
Troponin correlated with PERK (r = 0.39, p < 0.001)
Troponin is a standard clinical biomarker of myocardial injury, suggesting ER stress gene expression tracks with the degree of cardiac damage
Results
Inflammatory markers CRP and NLR showed weaker but statistically significant associations with ER stress-related gene expression.
Both C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) were associated with GRP78, PERK, and CHOP expression
These associations were described as 'weaker but significant' compared to troponin correlations
The findings suggest a relationship between systemic inflammation and peripheral ER stress marker elevation in cardiovascular disease
Specific correlation coefficients for CRP and NLR were not reported in the abstract
Results
Exploratory ROC analysis showed CHOP had the highest discriminatory performance for distinguishing acute cardiovascular disease patients from healthy controls.
ROC analysis was performed as an exploratory analysis for all three ER stress markers
CHOP outperformed both GRP78 and PERK in discriminating patients from controls
Specific AUC values were not provided in the abstract
The analysis compared 200 cardiovascular disease patients against 100 healthy controls
Authors note these are exploratory findings and further prospective studies are required to determine clinical significance
What This Means
This research suggests that when the heart is under acute stress — such as during a heart attack or heart failure — measurable changes occur in specific stress-response genes (GRP78, PERK, and CHOP) that can be detected in a simple blood test. These genes are part of the body's endoplasmic reticulum (ER) stress system, which is activated when cells are overwhelmed and struggle to function properly. The study found that all three stress markers were significantly elevated in patients with acute cardiovascular diseases compared to healthy individuals, with the most severe conditions (heart attacks and decompensated heart failure) showing the highest levels.
Importantly, these ER stress gene levels tracked closely with troponin — the standard blood test doctors already use to confirm heart muscle damage — suggesting that these markers reflect the severity of cardiac injury. Among the three genes studied, CHOP showed the strongest ability to distinguish patients with cardiovascular disease from healthy people, making it a potentially interesting target for future research into new diagnostic tools.
This research suggests that measuring ER stress genes in blood could one day complement existing tests for diagnosing and understanding acute heart conditions. However, the authors emphasize that these are preliminary findings from a relatively small, cross-sectional study, and larger prospective studies are needed before any clinical applications could be considered. The significance of this work lies in identifying a possible molecular pathway — ER stress — that connects cell-level dysfunction to the kinds of heart disease that remain the leading cause of death worldwide.
Oskay T, Oskay A, Özen M, Tekin I, Okta F, Elfiky A, et al.. (2026). Levels of ER Stress Markers GRP78, CHOP, and PERK in Cardiovascular Diseases.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167246