{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:18:56Z","timestamp":1783178336681,"version":"3.54.6"},"reference-count":21,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["NHBLI HL140268"],"award-info":[{"award-number":["NHBLI HL140268"]}]},{"name":"National Institutes of Health","award":["5R25GM061151-20"],"award-info":[{"award-number":["5R25GM061151-20"]}]},{"name":"National Institutes of Health","award":["U54-MD007600"],"award-info":[{"award-number":["U54-MD007600"]}]},{"name":"National Institutes of Health","award":["PR-INBRE P20GM103475"],"award-info":[{"award-number":["PR-INBRE P20GM103475"]}]},{"name":"NIGMS Undergraduate Research Training Initiative for Student Enhancement (RISE)","award":["NHBLI HL140268"],"award-info":[{"award-number":["NHBLI HL140268"]}]},{"name":"NIGMS Undergraduate Research Training Initiative for Student Enhancement (RISE)","award":["5R25GM061151-20"],"award-info":[{"award-number":["5R25GM061151-20"]}]},{"name":"NIGMS Undergraduate Research Training Initiative for Student Enhancement (RISE)","award":["U54-MD007600"],"award-info":[{"award-number":["U54-MD007600"]}]},{"name":"NIGMS Undergraduate Research Training Initiative for Student Enhancement (RISE)","award":["PR-INBRE P20GM103475"],"award-info":[{"award-number":["PR-INBRE P20GM103475"]}]},{"name":"Research Infrastructure Core components\u2014National Institute of Minority and Health Disparities (NIMHD)","award":["NHBLI HL140268"],"award-info":[{"award-number":["NHBLI HL140268"]}]},{"name":"Research Infrastructure Core components\u2014National Institute of Minority and Health Disparities (NIMHD)","award":["5R25GM061151-20"],"award-info":[{"award-number":["5R25GM061151-20"]}]},{"name":"Research Infrastructure Core components\u2014National Institute of Minority and Health Disparities (NIMHD)","award":["U54-MD007600"],"award-info":[{"award-number":["U54-MD007600"]}]},{"name":"Research Infrastructure Core components\u2014National Institute of Minority and Health Disparities (NIMHD)","award":["PR-INBRE P20GM103475"],"award-info":[{"award-number":["PR-INBRE P20GM103475"]}]},{"name":"Comprehensive Cancer Center","award":["NHBLI HL140268"],"award-info":[{"award-number":["NHBLI HL140268"]}]},{"name":"Comprehensive Cancer Center","award":["5R25GM061151-20"],"award-info":[{"award-number":["5R25GM061151-20"]}]},{"name":"Comprehensive Cancer Center","award":["U54-MD007600"],"award-info":[{"award-number":["U54-MD007600"]}]},{"name":"Comprehensive Cancer Center","award":["PR-INBRE P20GM103475"],"award-info":[{"award-number":["PR-INBRE P20GM103475"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet \u03b1 granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in platelet releasates. ADAM17 cuts TLT-1, suggesting that S136 is the C-terminal amino acid in sTLT-1. Our results revealed that for CAD patients, sTLT-1 levels did not differ significantly according to primary outcomes of death or major cardiac event; however, patients with left ventricular (LV) dysfunction had significantly lower plasma sTLT-1 levels as compared to those with normal LV function (981.62 \u00b1 1141 pg\/mL vs. 1247.48 \u00b1 1589 pg\/mL; p = 0.003). When patients were stratified based on sTLT-1 peak frequency distribution (544 pg\/mL), a significant association with congestive heart failure was identified (OR = 2.94; 1.040\u20138.282; p = 0.042), which could be explained by LV dysfunction.<\/jats:p>","DOI":"10.3390\/ijms241713632","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"13632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Characterization and Evaluation of the Soluble Triggering Receptor Expressed on Myeloid Cells-Like Transcript-1 in Stable Coronary Artery Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Zaida","family":"Bayr\u00f3n-Marrero","sequence":"first","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-6940","authenticated-orcid":false,"given":"Siobhan","family":"Branfield","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"},{"name":"Department of Biology, Oakland University, Rochester Hills, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Men\u00e9ndez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Nieves-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ospina","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadira","family":"Cantres-Rosario","sequence":"additional","affiliation":[{"name":"Translational Proteomics Center, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loyda M.","family":"Melendez","sequence":"additional","affiliation":[{"name":"Translational Proteomics Center, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USA"},{"name":"Department of Microbiology and Medical Zoology, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-0814","authenticated-orcid":false,"given":"Robert","family":"Hunter","sequence":"additional","affiliation":[{"name":"Retroviral Research Center, Universidad Central del Caribe, Bayam\u00f3n, PR 00960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelia","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Natural Sciences, Maryville College, Maryville, TN 37804, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger\u00f3nimo","family":"Maldonado-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Exercise Sciences Program, Universidad del Sagrado Coraz\u00f3n, San Juan, PR 00914, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-1822","authenticated-orcid":false,"given":"A. Valance","family":"Washington","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico\u2013Rio Piedras, San Juan, PR 00936, USA"},{"name":"Department of Biology, Oakland University, Rochester Hills, MI 48309, USA"},{"name":"William Beaumont School of Medicine, Oakland University, Rochester Hills, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1182\/blood-2018-03-841593","article-title":"Platelet-derived TLT-1 is a prognostic indicator in ALI\/ARDS and prevents tissue damage in the lungs in a mouse model","volume":"132","author":"Deal","year":"2018","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1080\/09537104.2021.1881948","article-title":"The enigmatic nature of the triggering receptor expressed in myeloid cells-1 (TLT-1)","volume":"32","author":"Branfield","year":"2021","journal-title":"Platelets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI36175","article-title":"TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans","volume":"119","author":"Washington","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1182\/blood-2010-05-283838","article-title":"Deciphering the human platelet sheddome","volume":"117","author":"Fong","year":"2011","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1182\/bloodadvances.2018017756","article-title":"TREM-like transcript 1: A more sensitive marker of platelet activation than P-selectin in humans and mice","volume":"2","author":"Smith","year":"2018","journal-title":"Blood Adv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/immu.200310033","article-title":"The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44","volume":"33","author":"Allcock","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.4049\/jimmunol.172.10.5838","article-title":"Cutting Edge: TREM-Like Transcript-1, a Platelet Immunoreceptor Tyrosine-Based Inhibition Motif Encoding Costimulatory Immunoreceptor that Enhances, Rather than Inhibits, Calcium Signaling via SHP-2","volume":"172","author":"Barrow","year":"2004","journal-title":"J. Immunol."},{"key":"ref_8","first-page":"457","article-title":"Early Markers of Atherosclerotic Disease in Individuals with Excess Weight and Dyslipidemia","volume":"106","author":"Menti","year":"2016","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1161\/01.CIR.96.4.1102","article-title":"Prospective Study of Hemostatic Factors and Incidence of Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"96","author":"Folsom","year":"1997","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1042\/CS20190999","article-title":"Elevated level of circulatory sTLT1 induces inflammation through SYK\/MEK\/ERK signalling in coronary artery disease","volume":"133","author":"Das","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shen, L., Yang, T., Xia, K., Yan, Z., Tan, J., Li, L., Qin, Y., and Shi, W. (2020). P-selectin (CD62P) and soluble TREM-like transcript-1 (sTLT-1) are associated with coronary artery disease: A case control study. BMC Cardiovasc. Disord., 20.","DOI":"10.1186\/s12872-020-01663-2"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1056\/NEJM199209033271001","article-title":"Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction","volume":"327","author":"Pfeffer","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJM199108013250508","article-title":"ACE Inhibitors\u2014A Cornerstone of the Treatment of Heart Failure","volume":"325","author":"Braunwald","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/0140-6736(92)92889-N","article-title":"Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions","volume":"340","author":"Yusuf","year":"1992","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1056\/NEJMoa042739","article-title":"Angiotensin-Converting\u2013Enzyme Inhibition in Stable Coronary Artery Disease","volume":"351","author":"Braunwald","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ijcard.2006.03.027","article-title":"Diastolic heart failure and left ventricular diastolic dysfunction: What we know, and what we don\u2019t know!","volume":"115","author":"Shammas","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12574-018-0405-5","article-title":"Echocardiographic assessment of left ventricular systolic function","volume":"17","author":"Klaeboe","year":"2018","journal-title":"J. Echocardiogr."},{"key":"ref_18","first-page":"971","article-title":"Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention","volume":"104","year":"2017","journal-title":"Heart"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiao, H., Wang, X., Li, S., Liu, Y., Cui, Y., and Deng, X. (2021). Advances in Biomarkers for Detecting Early Cancer Treatment-Related Cardiac Dysfunction. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.753313"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cardfail.2016.04.008","article-title":"Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs","volume":"22","author":"Mercurio","year":"2016","journal-title":"J. Card. Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/ehjci\/jeaa279","article-title":"Myocardial damage assessed by late gadolinium enhancement on cardiovascular magnetic resonance imaging in cancer patients treated with anthracyclines and\/or trastuzumab","volume":"22","author":"Modi","year":"2020","journal-title":"Eur. Hear. J. Cardiovasc. 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