{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T09:53:50Z","timestamp":1772272430363,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["LH2021H008"],"award-info":[{"award-number":["LH2021H008"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Harbin Medical University Postgraduate Research and Practical Innovation Project","award":["YJSCX2024-80HYD"],"award-info":[{"award-number":["YJSCX2024-80HYD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To address the forensic diagnostic challenge of distinguishing Anaphylactic Sudden Death (ASD) from Sudden Death from Coronary Heart Disease (SD-CHD), this study established Ldlr\u2212\/\u2212 mouse models of Atherosclerosis (AS) and ovalbumin-induced Anaphylaxis (AP). LC-MS\/MS-based serum proteomic analysis of Atherosclerosis (AS) and Anaphylaxis (AP) mice identified fibronectin 1 (FN1), platelet glycoprotein Ib\u03b1 chain (GP1BA), and platelet factor 4 (PF4) as candidate biomarkers. These candidates were validated by parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) in a combined AS + AP mouse model and in post-mortem human cardiac and bronchiolar epithelial tissue. In mice, serum FN1, GP1BA, and PF4 levels were significantly elevated in the AS group, whereas only FN1 was markedly downregulated in AP mice. In human tissues, FN1, GP1BA, and PF4 were all upregulated in Sudden death from coronary heart disease (SD-CHD) myocardial samples, with FN1 showing the greatest increase. In airway epithelium, FN1 was upregulated in anaphylactic sudden death (ASD) and anaphylactic sudden death (ASD) with Coronary Atherosclerosis (ASD + CAS) groups, while GP1BA was downregulated. These results indicate that FN1 serves as a key differential mouse serum biomarker, while PF4 and GP1BA aid in Sudden death from coronary heart disease (SD-CHD) diagnosis. Collectively, this multimarker, multilevel framework provides a molecular diagnostic strategy for the forensic identification of complex sudden death.<\/jats:p>","DOI":"10.3390\/ijms27052166","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:31:32Z","timestamp":1772098292000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Proteomic and Transcriptomic Profiling Identifies Candidate Biomarkers for Discriminating Anaphylactic from Cardiac Sudden Death"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhi-hao","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-qi","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-kang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhan-feng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0698-4074","authenticated-orcid":false,"given":"He","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Esposito, M., Montana, A., Liberto, A., Filetti, V., Nunno, N.D., Amico, F., Salerno, M., Loreto, C., and Sessa, F. (2021). Anaphylactic Death: A New Forensic Workflow for Diagnosis. Healthcare, 9.","DOI":"10.3390\/healthcare9020117"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.legalmed.2016.08.006","article-title":"Diagnosis of anaphylactic death in forensics: Review and future perspectives","volume":"22","author":"Cecchi","year":"2016","journal-title":"Leg. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/PAF.0000000000000972","article-title":"Association Between Cardiovascular Disease and Death by Anaphylaxis: A 20-Year Retrospective Study in Queensland, Australia","volume":"46","author":"Garland","year":"2025","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e28049","DOI":"10.1016\/j.heliyon.2024.e28049","article-title":"Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China","volume":"10","author":"Li","year":"2024","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1080\/00313020600820831","article-title":"Anaphylactic deaths in Auckland, New Zealand: A review of coronial autopsies from 1985 to 2005","volume":"38","author":"Low","year":"2006","journal-title":"Pathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12024-019-00134-1","article-title":"Medical and pathologic characteristics of fatal anaphylaxis: A Spanish nationwide 17-year series","volume":"15","year":"2019","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/PAF.0b013e3181c0e7bb","article-title":"Postmortem findings after anaphylactic reactions to drugs in Turkey","volume":"30","author":"Yilmaz","year":"2009","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2058738420950579","DOI":"10.1177\/2058738420950579","article-title":"Fatal food-induced anaphylaxis: Determination of tryptase and specific IgE on cadaveric blood samples. What else for a better methodological standard?","volume":"34","author":"Santurro","year":"2020","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40521-022-00326-1","article-title":"New Biomarkers in Anaphylaxis (Beyond Tryptase)","volume":"9","year":"2022","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/PAF.0000000000000572","article-title":"Reliable Postmortem Molecular Diagnosis of Anaphylaxis: Co-localization of Mast Cell Degranulation and Immunoglobulin E in Allergic Throat Tissues","volume":"41","author":"Wang","year":"2020","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102716","DOI":"10.1016\/j.legalmed.2025.102716","article-title":"A systematic review of the diagnostic value of post-mortem blood tryptase in fatal anaphylaxis: Assessment of sensitivity and specificity","volume":"78","author":"Pilia","year":"2025","journal-title":"Leg. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","article-title":"2023 ESC Guidelines for the management of acute coronary syndromes","volume":"44","author":"Byrne","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13597","DOI":"10.1038\/s41598-020-70501-4","article-title":"Kinetic modelling of myocardial necrosis biomarkers offers an easier, reliable and more acceptable assessment of infarct size","volume":"10","author":"Chadet","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"ytac353","DOI":"10.1093\/ehjcr\/ytac353","article-title":"Case report of elevation of high-sensitivity cardiac troponin T in the absence of cardiac involvement in immune checkpoint inhibitor-associated myositis","volume":"6","author":"Haaf","year":"2022","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sacco, M.A., Gualtieri, S., Grimaldi, G., Monterossi, M.D., Aquila, V.R., Tarallo, A.P., Verrina, M.C., Ranno, F., Gratteri, S., and Aquila, I. (2024). The Role of Cardiac Troponins in Postmortem Diagnosis of Myocardial Ischemia: A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010105"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.amjcard.2025.08.036","article-title":"Incidence of Elevated Cardiac Biomarkers in Patients Presenting to the Emergency Department With Allergic Symptoms: Implications for the Diagnosis of Kounis Syndrome","volume":"258","author":"Anastasopoulou","year":"2026","journal-title":"Am. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Isail\u0103, O.M., Ion, O.M., Luta, R., Catinas, R., Ionita, A., Haisan, D., and Hostiuc, S. (2024). Postmortem Immunohistochemical Findings in Early Acute Myocardial Infarction: A Systematic Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147625"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Iadarola, P., and Viglio, S. (2024). Mass Spectrometric Proteomics 2.0. Int. J. Mol. Sci., 25.","DOI":"10.3390\/books978-3-7258-0636-2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1136\/archdischild-2019-317434","article-title":"What is proteomics?","volume":"106","author":"McArdle","year":"2021","journal-title":"Arch. Dis. Child. Educ. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Romero, D., S\u00e1nchez-Rodr\u00edguez, E., Osuna, E., Sib\u00f3n, A., Mart\u00ednez-Villanueva, M., Noguera-Velasco, J.A., and P\u00e9rez-C\u00e1rceles, M.D. (2020). Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and \u03b1-1Antitrypsin, Pilot Study. Diagnostics, 10.","DOI":"10.3390\/diagnostics10100747"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Huang, Y., Qiu, H., Chen, Q., Meng, Z., Qiao, D., and Yue, X. (2024). Exploring Potential Diagnostic Biomarkers for Mechanical Asphyxia in the Heart Based on Proteomics Technology. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312710"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Marrone, A., La Russa, D., Barberio, L., Murfuni, M.S., Gaspari, M., and Pellegrino, D. (2023). Forensic Proteomics for the Discovery of New post mortem Interval Biomarkers: A Preliminary Study. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914627"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102529","DOI":"10.1016\/j.fsigen.2021.102529","article-title":"Forensic proteomics","volume":"54","author":"Parker","year":"2021","journal-title":"Forensic Sci. Int. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00216-024-05674-2","article-title":"Proteomics for forensic identification of saliva and vomit in a case of alleged rape","volume":"417","author":"Pieri","year":"2025","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102302","DOI":"10.1016\/j.legalmed.2023.102302","article-title":"Identification of differentially expressed proteins in heart of mouse death from smother based on label-free proteomics","volume":"65","author":"Zheng","year":"2023","journal-title":"Leg. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1475-2840-13-23","article-title":"An accelerated mouse model for atherosclerosis and adipose tissue inflammation","volume":"13","author":"Neuhofer","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115303","DOI":"10.1016\/j.addr.2024.115303","article-title":"Delivery technologies for therapeutic targeting of fibronectin in autoimmunity and fibrosis applications","volume":"209","author":"Bonadio","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C1212","DOI":"10.1152\/ajpcell.00633.2023","article-title":"The role of fibronectin in mediating cell migration","volume":"326","author":"Longstreth","year":"2024","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.addr.2020.09.005","article-title":"Fibronectin in development and wound healing","volume":"170","author":"Patten","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Peng, L., Deng, H., Li, J., Lu, G., and Zhai, Y.S. (2023). Plasma Fibronectin as a Novel Predictor of Coronary Heart Disease: A Retrospective Study. J. Cardiovasc. Dev. Dis., 10.","DOI":"10.3390\/jcdd10100415"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/0022-2828(95)90067-5","article-title":"Fibronectin expression during physiological and pathological cardiac growth","volume":"27","author":"Farhadian","year":"1995","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, C., Meng, X., Wang, L., and Dai, X. (2023). Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-\u03b2\/Smad signaling pathway. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1092148"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2400741","DOI":"10.1002\/advs.202400741","article-title":"SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling","volume":"11","author":"Liu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.ajpath.2023.09.014","article-title":"Exogenous Transforming Growth Factor-\u03b21 and Its Helminth-Derived Mimic Attenuate the Heart\u2019s Inflammatory Response to Ischemic Injury and Reduce Mature Scar Size","volume":"194","author":"Redgrave","year":"2024","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41569-024-01088-w","article-title":"Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches","volume":"22","author":"Schotten","year":"2025","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jaci.2010.10.021","article-title":"The extra domain A of fibronectin is essential for allergen-induced airway fibrosis and hyperresponsiveness in mice","volume":"127","author":"Kohan","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jaci.2022.06.012","article-title":"Modulation of IL-4\/IL-13 cytokine signaling in the context of allergic disease","volume":"150","author":"Shankar","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yoshie, S., Murono, S., and Hazama, A. (2023). Approach for Elucidating the Molecular Mechanism of Epithelial to Mesenchymal Transition in Fibrosis of Asthmatic Airway Remodeling Focusing on Cl\u2212 Channels. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010289"},{"key":"ref_39","first-page":"1969","article-title":"Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus","volume":"135","author":"Calzavarini","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.pathol.2021.10.008","article-title":"Laboratory testing for platelet factor 4 antibodies: Differential utility for diagnosis\/exclusion of heparin induced thrombocytopenia versus suspected vaccine induced thrombotic thrombocytopenia","volume":"54","author":"Favaloro","year":"2022","journal-title":"Pathology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1055\/s-0044-1789183","article-title":"Platelet-type von Willebrand disease: Complex pathophysiology and insights on novel therapeutic and diagnostic strategies","volume":"51","author":"Fu","year":"2025","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13020-021-00424-3","article-title":"Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy","volume":"16","author":"Xu","year":"2021","journal-title":"Chin. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"154157","DOI":"10.1016\/j.cyto.2017.09.013","article-title":"Platelet-derived chemokines in inflammation and atherosclerosis","volume":"122","author":"Bakogiannis","year":"2019","journal-title":"Cytokine"},{"key":"ref_44","first-page":"340","article-title":"Elevation of platelet factor four in acute myocardial infarction: Measurement by radioimmunoassay","volume":"91","author":"Handin","year":"1978","journal-title":"J. Lab. Clin. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1074\/mcp.M115.055731","article-title":"Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic (MI) injury","volume":"15","author":"Cheow","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1111\/1556-4029.70147","article-title":"Beyond the numbers: Critical analysis of the role of postmortem tryptase in the forensic diagnosis of anaphylaxis","volume":"70","author":"Tomassini","year":"2025","journal-title":"J. Forensic Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.jaci.2009.09.054","article-title":"Differential roles for the IL-9\/IL-9 receptor \u03b1-chain pathway in systemic and oral antigen-induced anaphylaxis","volume":"125","author":"Osterfeld","year":"2010","journal-title":"J. Allergy Clin. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:14:23Z","timestamp":1772255663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052166"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052166","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]}}}