{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:10:20Z","timestamp":1772244620714,"version":"3.50.1"},"reference-count":50,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"crossref","award":["0404\/2019"],"award-info":[{"award-number":["0404\/2019"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Estrogen is an important ovarian hormone with anti-atherogenic and cardioprotective effects. Postmenopausal women have lower estrogen levels, associated with significantly higher risks of coronary heart disease (CHD) and CHD-related death. Effective biomarkers for the diagnosis, prediction, and treatment of CHD are needed to address this problem and thus reduce the mortality due to CHD in postmenopausal women. We recently reported that the <jats:italic>PPBP<\/jats:italic> and <jats:italic>DEFA1\/DEFA3<\/jats:italic> genes may be feasible synergistic biomarkers for CHD risk in Thai men with hyperlipidemia. The <jats:italic>PPBP<\/jats:italic> gene encodes pro-platelet basic protein (PPBP) from activated platelets, and <jats:italic>DEFA1\/DEFA3<\/jats:italic> encodes human neutrophil peptides (HNP) 1\u20133, mainly produced by activated neutrophils. Both platelets and neutrophils are involved in chronic inflammation during the development of atherogenesis and CHD. This study investigated the potential roles of <jats:italic>PPBP<\/jats:italic> and <jats:italic>DEFA1\/DEFA3<\/jats:italic> and their proteins as biomarkers for CHD risk in postmenopausal Thai women.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>This cross-sectional study enrolled 90 postmenopausal Thai women, including 12 healthy controls (N), 18 patients with hyperlipidemia (H), and 21 patients diagnosed with CHD. The remaining 39 women were receiving cholesterol-lowering drugs for hyperlipidemia (HD) were excluded from the study. All CHD patients underwent coronary bypass grafting or coronary angioplasty. <jats:italic>PPBP<\/jats:italic> and <jats:italic>DEFA1\/DEFA3<\/jats:italic> mRNA expression levels in peripheral blood mononuclear cells isolated from heparinized blood were determined by quantitative reverse-transcription polymerase chain reaction. Levels of PPBP and HNP-1\u20133 proteins in corresponding plasma samples were assessed by enzyme-linked immunosorbent assay. Differences in parameters were compared among groups and correlations between parameters and clinical manifestations were analyzed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>PPBP mRNA and protein levels were significantly increased in the CHD group compared with the N and H groups. In contrast, <jats:italic>DEFA1\/DEFA3<\/jats:italic> mRNA and HNP-1\u20133 protein levels did not differ significantly among the groups. None of the levels were associated with any of the clinical parameters analyzed in this study.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The results indicate that gene and protein expression levels of PPBP, but not <jats:italic>DEFA1\/DEFA3<\/jats:italic>, and HNP-1\u20133, may be feasible biomarkers for assessing CHD risk in postmenopausal Thai women with hyperlipidemia.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.13615","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T08:51:33Z","timestamp":1655455893000},"page":"e13615","source":"Crossref","is-referenced-by-count":11,"title":["<i>PPBP<\/i> gene as a biomarker for coronary heart disease risk in postmenopausal Thai women"],"prefix":"10.7717","volume":"10","author":[{"given":"Chayasin","family":"Mansanguan","sequence":"first","affiliation":[{"name":"Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaowapa","family":"Maneerat","sequence":"additional","affiliation":[{"name":"Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"issue":"14","key":"10.7717\/peerj.13615\/ref-1","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1093\/hmg\/ddi209","article-title":"Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3","volume":"14","author":"Aldred","year":"2005","journal-title":"Human Molecular Genetics"},{"issue":"7","key":"10.7717\/peerj.13615\/ref-2","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1093\/eurheartj\/ehn018","article-title":"Risk factors for myocardial infarction in women and men: insights from the INTERHEART study","volume":"29","author":"Anand","year":"2008","journal-title":"European Heart Journal"},{"issue":"3","key":"10.7717\/peerj.13615\/ref-3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1097\/SHK.0b013e3181b2b36b","article-title":"Gender differences in inflammatory markers in children","volume":"33","author":"Casimir","year":"2010","journal-title":"Shock"},{"issue":"10","key":"10.7717\/peerj.13615\/ref-4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/1458320","article-title":"Identification of combinations of plasma lncRNAs and mRNAs as potential biomarkers for precursor lesions and early gastric cancer","volume":"2022","author":"Chen","year":"2022","journal-title":"Journal of Oncology"},{"issue":"2","key":"10.7717\/peerj.13615\/ref-5","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1160\/TH07-06-0387","article-title":"Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intima","volume":"99","author":"Dorweiler","year":"2008","journal-title":"Thrombosis and Haemostasis"},{"issue":"3","key":"10.7717\/peerj.13615\/ref-6","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3109\/09537104.2015.1083543","article-title":"Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction","volume":"27","author":"Eicher","year":"2016","journal-title":"Platelets"},{"issue":"2","key":"10.7717\/peerj.13615\/ref-7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.5551\/jat.10.63","article-title":"Inflammatory reactions in the pathogenesis of atherosclerosis","volume":"10","author":"Fan","year":"2003","journal-title":"Journal of Atherosclerosis and Thrombosis"},{"issue":"4","key":"10.7717\/peerj.13615\/ref-8","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/0952-7915(94)90145-7","article-title":"Defensins","volume":"6","author":"Ganz","year":"1994","journal-title":"Current Opinion in Immunology"},{"issue":"8","key":"10.7717\/peerj.13615\/ref-9","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1161\/CIRCRESAHA.116.307547","article-title":"Cardiovascular disease in women: clinical perspectives","volume":"118","author":"Garcia","year":"2016","journal-title":"Circulation Research"},{"issue":"11","key":"10.7717\/peerj.13615\/ref-10","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1161\/ATVBAHA.108.169417","article-title":"Platelet chemokines in vascular disease","volume":"28","author":"Gleissner","year":"2008","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"issue":"25 Pt B","key":"10.7717\/peerj.13615\/ref-11","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1016\/j.jacc.2013.11.005","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College Of Cardiology\/American Heart Association task force on practice guidelines","volume":"63","author":"Goff","year":"2014","journal-title":"Journal of the American College of Cardiology"},{"issue":"17","key":"10.7717\/peerj.13615\/ref-12","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1016\/j.jacc.2022.02.036","article-title":"Systematic review of physical activity trajectories and mortality in patients with coronary artery disease","volume":"79","author":"Gonzalez-Jaramillo","year":"2022","journal-title":"Journal of the American College of Cardiology"},{"key":"10.7717\/peerj.13615\/ref-13","doi-asserted-by":"publisher","first-page":"122705","DOI":"10.1016\/j.talanta.2021.122705","article-title":"Simultaneous determination of CXCL7 chemokine and MMP3 metalloproteinase as biomarkers for rheumatoid arthritis","volume":"234","author":"Guerrero","year":"2021","journal-title":"Talanta"},{"issue":"28","key":"10.7717\/peerj.13615\/ref-14","doi-asserted-by":"publisher","first-page":"16481","DOI":"10.1073\/pnas.2003603117","article-title":"Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism","volume":"117","author":"Gupta","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"16","key":"10.7717\/peerj.13615\/ref-15","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1056\/NEJMra043430","article-title":"Inflammation, atherosclerosis, and coronary artery disease","volume":"352","author":"Hansson","year":"2005","journal-title":"New England Journal of Medicine"},{"issue":"10","key":"10.7717\/peerj.13615\/ref-16","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1101\/gr.6.10.986","article-title":"Real time quantitative PCR","volume":"6","author":"Heid","year":"1996","journal-title":"Genome Research"},{"issue":"4","key":"10.7717\/peerj.13615\/ref-17","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1161\/01.RES.0000259043.42571.68","article-title":"Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury","volume":"100","author":"Hristov","year":"2007","journal-title":"Circulation Research"},{"issue":"5845","key":"10.7717\/peerj.13615\/ref-18","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1126\/science.1146304","article-title":"Dynamic visualization of thrombopoiesis within bone marrow","volume":"317","author":"Junt","year":"2007","journal-title":"Science"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0002-8703(96)90384-1","article-title":"Band neutrophil count and the presence and severity of coronary atherosclerosis","volume":"132","author":"Kawaguchi","year":"1996","journal-title":"American Heart Journal"},{"issue":"11","key":"10.7717\/peerj.13615\/ref-20","doi-asserted-by":"publisher","first-page":"5879","DOI":"10.7314\/APJCP.2012.13.11.5879","article-title":"Quantitative real-time RT-PCR of ITGA7, SVEP1, TNS1, LPHN3, SEMA3G, KLB and MMP13 mRNA expression in breast cancer","volume":"13","author":"Kotepui","year":"2012","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"issue":"2","key":"10.7717\/peerj.13615\/ref-21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.jvs.2005.10.019","article-title":"Neutrophil antimicrobial peptide alpha-defensin causes endothelial dysfunction in porcine coronary arteries","volume":"43","author":"Kougias","year":"2006","journal-title":"Journal of Vascular Surgery"},{"issue":"11","key":"10.7717\/peerj.13615\/ref-22","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.humimm.2014.09.014","article-title":"Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels","volume":"75","author":"Li","year":"2014","journal-title":"Human Immunology"},{"issue":"9","key":"10.7717\/peerj.13615\/ref-23","doi-asserted-by":"publisher","first-page":"e23366","DOI":"10.1002\/jcla.23366","article-title":"Increased CCL24 and CXCL7 levels in the cerebrospinal fluid of patients with neurosyphilis","volume":"34","author":"Li","year":"2020","journal-title":"Journal of Clinical Laboratory Analysis"},{"issue":"9","key":"10.7717\/peerj.13615\/ref-24","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in atherosclerosis","volume":"32","author":"Libby","year":"2012","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"issue":"4","key":"10.7717\/peerj.13615\/ref-25","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.ygeno.2005.06.003","article-title":"Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23","volume":"86","author":"Linzmeier","year":"2005","journal-title":"Genomics"},{"issue":"2","key":"10.7717\/peerj.13615\/ref-26","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/sj.cdd.4401320","article-title":"Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis","volume":"11","author":"Maianski","year":"2004","journal-title":"Cell Death and Differentiation"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-27","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12944-017-0471-0","article-title":"PPBP and DEFA1\/DEFA3 genes in hyperlipidaemia as feasible synergistic inflammatory biomarkers for coronary heart disease","volume":"16","author":"Maneerat","year":"2017","journal-title":"Lipids in Health and Disease"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-28","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12944-016-0285-5","article-title":"Increased alpha-defensin expression is associated with risk of coronary heart disease: a feasible predictive inflammatory biomarker of coronary heart disease in hyperlipidemia patients","volume":"15","author":"Maneerat","year":"2016","journal-title":"Lipids in Health and Disease"},{"issue":"9","key":"10.7717\/peerj.13615\/ref-29","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1161\/01.RES.0000264509.36234.51","article-title":"Clinical aspects of platelet inhibitors and thrombus formation","volume":"100","author":"Meadows","year":"2007","journal-title":"Circulation Research"},{"key":"10.7717\/peerj.13615\/ref-30","doi-asserted-by":"publisher","first-page":"744459","DOI":"10.3389\/fmolb.2021.744459","article-title":"Potential biomarkers to predict acute ischemic stroke in type 2 diabetes","volume":"8","author":"Moin","year":"2021","journal-title":"Frontiers in Molecular Biosciences"},{"issue":"23","key":"10.7717\/peerj.13615\/ref-31","doi-asserted-by":"publisher","first-page":"2894","DOI":"10.1161\/01.CIR.0000042674.89762.20","article-title":"Neutrophil infiltration of culprit lesions in acute coronary syndromes","volume":"106","author":"Naruko","year":"2002","journal-title":"Circulation"},{"key":"10.7717\/peerj.13615\/ref-32","doi-asserted-by":"publisher","first-page":"850815","DOI":"10.3389\/fphar.2022.850815","article-title":"The effects of menopause hormone therapy on lipid profile in postmenopausal women: a systematic review and meta-analysis","volume":"13","author":"Nie","year":"2022","journal-title":"Frontiers in Pharmacology"},{"issue":"11","key":"10.7717\/peerj.13615\/ref-33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3389\/fimmu.2015.00098","article-title":"Platelets in inflammation and atherogenesis","volume":"6","author":"Nording","year":"2015","journal-title":"Frontiers in Immunology"},{"issue":"2\u20133","key":"10.7717\/peerj.13615\/ref-34","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1159\/000105681","article-title":"Leukocyte count and vascular risk in symptomatic intracranial atherosclerosis","volume":"24","author":"Ovbiagele","year":"2007","journal-title":"Cerebrovascular Diseases"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-35","doi-asserted-by":"publisher","first-page":"145987","DOI":"10.1016\/j.gene.2021.145987","article-title":"Exploring potential genes and pathways related to calcific aortic valve disease","volume":"808","author":"Qiao","year":"2022","journal-title":"Gene"},{"key":"10.7717\/peerj.13615\/ref-36","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12967-019-1962-8","article-title":"Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion","volume":"17","author":"Qin","year":"2019","journal-title":"Journal of Translational Medicine"},{"issue":"5","key":"10.7717\/peerj.13615\/ref-37","doi-asserted-by":"publisher","first-page":"H1817","DOI":"10.1152\/ajpheart.00472.2008","article-title":"Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases","volume":"295","author":"Quinn","year":"2008","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-38","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1095\/biolreprod54.1.183","article-title":"Ovarian steroid hormones regulate granulocyte-macrophage colony-stimulating factor synthesis by uterine epithelial cells in the mouse","volume":"54","author":"Robertson","year":"1996","journal-title":"Biology of Reproduction"},{"key":"10.7717\/peerj.13615\/ref-39","volume-title":"Fundamentals of biostatistics","author":"Rosner","year":"2000"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11883-022-00980-5","article-title":"Sex differences in coronary atherosclerosis","volume":"24","author":"Sato","year":"2022","journal-title":"Current Atherosclerosis Reports"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-41","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s12868-014-0130-6","article-title":"Social stress increases expression of hemoglobin genes in mouse prefrontal cortex","volume":"15","author":"Stankiewicz","year":"2014","journal-title":"BMC Neuroscience"},{"issue":"8\u20139","key":"10.7717\/peerj.13615\/ref-42","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1016\/j.imbio.2017.05.007","article-title":"Ovarian hormones in innate inflammation","volume":"222","author":"Stubelius","year":"2017","journal-title":"Immunobiology"},{"key":"10.7717\/peerj.13615\/ref-43","doi-asserted-by":"publisher","first-page":"101228","DOI":"10.1016\/j.cpcardiol.2022.101228","article-title":"Coronary artery disease in South Asian patients: cardiovascular risk factors, pathogenesis and treatments. [Online ahead of print 29 April 2022]","author":"Sucato","year":"2022","journal-title":"Current Problems in Cardiology"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-44","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1161\/ATVBAHA.107.154807","article-title":"Accumulation of myeloperoxidase-positive neutrophils in atherosclerotic lesions in LDLR-\/- mice","volume":"28","author":"van Leeuwen","year":"2008","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.7717\/peerj.13615\/ref-45","doi-asserted-by":"publisher","first-page":"870176","DOI":"10.3389\/fcvm.2022.870176","article-title":"The admission (neutrophil+monocyte)\/lymphocyte ratio is an independent predictor for in-hospital mortality in patients with acute myocardial infarction","volume":"9","author":"Wang","year":"2022","journal-title":"Frontiers in Cardiovascular Medicine"},{"issue":"11","key":"10.7717\/peerj.13615\/ref-46","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1038\/nm.2538","article-title":"Atherosclerosis: current pathogenesis and therapeutic options","volume":"17","author":"Weber","year":"2011","journal-title":"Nature Medicine"},{"issue":"1","key":"10.7717\/peerj.13615\/ref-47","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13613-021-00899-1","article-title":"Platelet activation in critically ill COVID-19 patients","volume":"11","author":"Yatim","year":"2021","journal-title":"Annals of Intensive Care"},{"issue":"4","key":"10.7717\/peerj.13615\/ref-48","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1136\/annrheumdis-2014-206921","article-title":"Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis","volume":"75","author":"Yeo","year":"2016","journal-title":"Annals of the Rheumatic Diseases"},{"key":"10.7717\/peerj.13615\/ref-49","doi-asserted-by":"publisher","first-page":"744304","DOI":"10.3389\/fgene.2021.744304","article-title":"Association of a novel prognosis model with tumor mutation burden and tumor-infiltrating immune cells in thyroid carcinoma","volume":"12","author":"Zhang","year":"2021b","journal-title":"Frontiers in Genetics"},{"key":"10.7717\/peerj.13615\/ref-50","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.bbrc.2021.08.087","article-title":"PPBP as a marker of diabetic nephropathy podocyte injury via bioinformatics analysis","volume":"577","author":"Zhang","year":"2021a","journal-title":"Biochemical and Biophysical Research Communications"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/13615.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13615.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13615.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13615.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T08:51:40Z","timestamp":1655455900000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/13615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":50,"alternative-id":["10.7717\/peerj.13615"],"URL":"https:\/\/doi.org\/10.7717\/peerj.13615","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,17]]},"article-number":"e13615"}}