{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:36:04Z","timestamp":1786700164076,"version":"build-2736575974"},"reference-count":24,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Personalized Innovative Medicine Competence Center-2","award":["BG16RFPR002-1.014-0007-C01"],"award-info":[{"award-number":["BG16RFPR002-1.014-0007-C01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013Wallis test followed by Dunn\u2019s post hoc test with Bonferroni adjustment. Significant differences in GRP78, PERK, and CHOP expression were observed among the study groups (all p &lt; 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms27167246","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:01Z","timestamp":1786698241000},"page":"7246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Levels of ER Stress Markers GRP78, CHOP, and PERK in Cardiovascular Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"T\u00fclay","family":"Oskay","sequence":"first","affiliation":[{"name":"Department of Cardiology, Denizli State Hospital, 20010 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4373-6280","authenticated-orcid":false,"given":"Alten","family":"Oskay","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mert","family":"\u00d6zen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-920X","authenticated-orcid":false,"given":"Is\u0131k","family":"Tekin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0759-3211","authenticated-orcid":false,"given":"F\u0131rat","family":"Okta","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-6240","authenticated-orcid":false,"given":"Abdo A.","family":"Elfiky","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-9471","authenticated-orcid":false,"given":"Murat","family":"Seyit","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atakan","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"Ak\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-4615","authenticated-orcid":false,"given":"Ibrahim","family":"T\u00fcrk\u00e7\u00fcer","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-1439","authenticated-orcid":false,"given":"Gergana","family":"Lengerova","sequence":"additional","affiliation":[{"name":"Microbiology Laboratory, Department of Microbiology, Virology, Clinical Laboratory and Immunology, Military Medical Academy of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-3299","authenticated-orcid":false,"given":"Martina","family":"Bozhkova","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elissay Yanev\u201d, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Center of Competence-Personalized Innovative Medicine, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-5682","authenticated-orcid":false,"given":"Steliyan","family":"Petrov","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elissay Yanev\u201d, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-0436","authenticated-orcid":false,"given":"Aylin","family":"K\u00f6seler","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Pamukkale University, 20160 Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Favero, G., Bonomini, F., Gian\u00f2, M., and Rezzani, R. (2023). Endoplasmic Reticulum Involvement in Heart Injury: An Overview. Biochemistry, IntechOpen.","DOI":"10.5772\/intechopen.111772"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1007\/s11010-023-04856-3","article-title":"Myocardial Infarction Elevates Endoplasmic Reticulum Stress and Protein Aggregation in Heart as Well as Brain","volume":"479","author":"Mainali","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.21873\/invivo.11640","article-title":"Predictive Value of Endoplasmic Reticulum Stress Markers in Low Ejection Fractional Heart Failure","volume":"33","author":"Mansur","year":"2019","journal-title":"In Vivo"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Huang, X., Jiang, F., Ma, Y., Zhu, K., Wang, Z., Hua, Z., Yu, J., and Zhang, L. (2024). A Bibliometric Analysis of Endoplasmic Reticulum Stress and Atherosclerosis. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1392454"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10435","DOI":"10.1038\/s41598-021-89713-3","article-title":"Heme Cytotoxicity Is the Consequence of Endoplasmic Reticulum Stress in Atherosclerotic Plaque Progression","volume":"11","author":"Hendrik","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rao, Z., Zheng, Y., Xu, L., Wang, Z., Zhou, Y., Chen, M., Dong, N., Cai, Z., and Li, F. (2022). Endoplasmic Reticulum Stress and Pathogenesis of Vascular Calcification. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.918056"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105629","DOI":"10.1016\/j.phrs.2021.105629","article-title":"The Ameliorative Effect of Terpinen-4-Ol on ER Stress-Induced Vascular Calcification Depends on SIRT1-Mediated Regulation of PERK Acetylation","volume":"170","author":"Zhang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s00223-023-01096-x","article-title":"Bone and the Unfolded Protein Response: In Sickness and in Health","volume":"113","author":"Iyer","year":"2023","journal-title":"Calcif. Tissue Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, W., Gong, Y., and Yan, L. (2023). ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review. Biomolecules, 13.","DOI":"10.3390\/biom13071050"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s10020-022-00586-2","article-title":"Transcription Factors: Key Regulatory Targets of Vascular Smooth Muscle Cell in Atherosclerosis","volume":"29","author":"Jiang","year":"2023","journal-title":"Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Keylani, K., Mojeni, F.A., Khalaji, A., Rasouli, A., Aminzade, D., Karimi, M.A., Sanaye, P.M., Khajevand, N., Nemayandeh, N., and Poudineh, M. (2023). Endoplasmic Reticulum as a Target in Cardiovascular Diseases: Is There a Role for Flavonoids?. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1027633"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11906-024-01300-9","article-title":"Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure","volume":"26","author":"Balhara","year":"2024","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.33549\/physiolres.934797","article-title":"Pharmacological Inhibition of EIF2\u03b1 Phosphorylation by Integrated Stress Response Inhibitor (ISRIB) Ameliorates Vascular Calcification in Rats","volume":"71","author":"Dong","year":"2022","journal-title":"Physiol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s00018-024-05286-0","article-title":"Redox Regulation of UPR Signalling and Mitochondrial ER Contact Sites","volume":"81","author":"Samali","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s12276-021-00560-8","article-title":"The Aftermath of the Interplay between the Endoplasmic Reticulum Stress Response and Redox Signaling","volume":"53","author":"Bhattarai","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ni, L., Yang, L., and Lin, Y. (2024). Recent Progress of Endoplasmic Reticulum Stress in the Mechanism of Atherosclerosis. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1413441"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10495","DOI":"10.2147\/JIR.S494438","article-title":"Identification of Diagnostically Relevant Biomarkers in Patients with Coronary Artery Disease by Comprehensive Analysis","volume":"17","author":"Wu","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s10020-023-00706-6","article-title":"Unveiling the Dark Side of Glucose-Regulated Protein 78 (GRP78) in Cancers and Other Human Pathology: A Systematic Review","volume":"29","author":"Akinyemi","year":"2023","journal-title":"Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11980","DOI":"10.1038\/s41598-024-62764-y","article-title":"A Novel BAG5 Variant Impairs the ER Stress Response Pathway, Causing Dilated Cardiomyopathy and Arrhythmia","volume":"14","author":"Wongong","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"176530","DOI":"10.1016\/j.ejphar.2024.176530","article-title":"Potential Targets for the Treatment of MI: GRP75-Mediated Ca2+transfer in MAM","volume":"971","author":"Zhang","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Qin, C., Wang, Y., Zhang, Y., Zhu, Y., Wang, Y., and Cao, F. (2023). Transcriptome-Wide Analysis Reveals the Molecular Mechanisms of Cannabinoid Type II Receptor Agonists in Cardiac Injury Induced by Chronic Psychological Stress. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1095428"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s10020-024-00869-w","article-title":"Endoplasmic Reticulum Stress Signaling Modulates Ischemia\/Reperfusion Injury in the Aged Heart by Regulating Mitochondrial Maintenance","volume":"30","author":"Zhang","year":"2024","journal-title":"Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Oskay, A., Oskay, T., Ayd\u0131n, V.K., Eser, \u00d6., Seyit, M., Tekin, I., \u00d6zen, M., Y\u0131lmaz, A., T\u00fcrk\u00e7\u00fcer, \u0130., and Lengerova, G. (2026). CYP450 Metabolizer Phenotypes in a Turkish Emergency Cardiac Patient Cohort: A Descriptive Pharmacogenomic Study. Pharmaceuticals, 19.","DOI":"10.3390\/ph19060812"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.15407\/ubj95.01.044","article-title":"Cardioprotective Effect of Ginger in a Rat Model of Myocardial Damage and Its Possible Intervention in PERK-ATF4-CHOP-PUMA Apoptotic Pathway","volume":"95","author":"Mohammed","year":"2023","journal-title":"Ukr. Biochem. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:05:10Z","timestamp":1786698310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":24,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167246"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167246","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}