{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:31:01Z","timestamp":1789605061465,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"Grant for Scientific Research of the Medical University of Silesia","doi-asserted-by":"publisher","award":["PCN-1-203\/N\/2\/K"],"award-info":[{"award-number":["PCN-1-203\/N\/2\/K"]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aortic stenosis (AS) is a progressive valvular heart disease characterized by fibrocalcific remodeling, inflammation, and hemodynamic disturbances. Serum biomarkers may indirectly reflect these processes. Autotaxin (ATX) and lysophosphatidic acid (LPA) have been implicated in osteogenic differentiation of valvular interstitial cells, while growth differentiation factor-15 (GDF-15) reflects cellular stress and vascular changes. Thrombomodulin (TM) indicates endothelial injury and interacts with thrombin. This study aimed to evaluate biomarkers focusing on serum ATX, LPA, GDF-15, and TM levels and flow-mediated dilatation (FMD) in patients with AS. Overall, 149 patients were included in the study: 86 consecutive patients with AS hospitalized due to qualification for invasive treatment of AS and 63 controls. The clinical characteristics, echocardiographic data, FMD, and the following biomarkers\u2014ATX, LPA, GDF-15, and TM\u2014were included in the analysis. AS patients presented increased serum levels of ATX, GDF-15, and TM as compared to the controls. Differences in LPA levels were not statistically significant. FMD values were significantly lower in AS patients. The biomarkers mentioned above and FMD correlated with AS severity. There were no differences in both biomarkers\u2019 serum levels and FMD regarding the hemodynamic AS phenotype. GDF-15 serum level was a risk factor for all-cause mortality and MACCE in the 12-month follow-up.<\/jats:p>","DOI":"10.3390\/ijms26104873","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T11:54:26Z","timestamp":1747655666000},"page":"4873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biomarkers of Calcification, Endothelial Injury, and Platelet-Endothelial Interaction in Patients with Aortic Valve Stenosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Pawe\u0142","family":"Ba\u0144ka","sequence":"first","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-1928","authenticated-orcid":false,"given":"Klaudia","family":"M\u0119cka","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianna","family":"Berger-Kucza","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1831","authenticated-orcid":false,"given":"Karolina","family":"Wrona-Kolasa","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rybicka-Musialik","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Nowak","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"El\u017cbieciak","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Mizia-Szubryt","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-6090","authenticated-orcid":false,"given":"Tomasz","family":"Francuz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Lelek","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-9586","authenticated-orcid":false,"given":"Agnieszka","family":"Kosowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5343-1205","authenticated-orcid":false,"given":"Wojciech","family":"Garczorz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-2665","authenticated-orcid":false,"given":"Tomasz","family":"Bochenek","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-9510","authenticated-orcid":false,"given":"Andrzej","family":"Swinarew","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology, University of Silesia, 41-500 Chorz\u00f3w, Poland"},{"name":"Institute of Sport Science, The Jerzy Kukuczka Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Paluch","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"},{"name":"Department of Laryngology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1151-8385","authenticated-orcid":false,"given":"Maciej","family":"Wybraniec","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6907-2799","authenticated-orcid":false,"given":"Katarzyna","family":"Mizia-Stec","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, 40-635 Katowice, Poland"},{"name":"Centre of the European Reference Network for Rare, Low Prevalence or Complex Diseases of the Heart (ERN GUARD Heart), 40-635 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.suc.2022.01.008","article-title":"Epidemiology of Valvular Heart Disease","volume":"102","author":"Peters","year":"2022","journal-title":"Surg. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ba\u0144ka, P., Wybraniec, M., Bochenek, T., Gruchlik, B., Burchacka, A., Swinarew, A., and Mizia-Stec, K. (2023). Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function. J. Clin. Med., 12.","DOI":"10.3390\/jcm12196301"},{"key":"ref_4","first-page":"888","article-title":"Interaction of Autotaxin with Lipoprotein(a) in Patients with Calcific Aortic Valve Stenosis","volume":"5","author":"Bourgeois","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.amjcard.2022.09.029","article-title":"Growth Differentiation Factor-15 as a Predictor of Functional Capacity, Frailty, and Ventricular Dysfunction in Patients with Aortic Stenosis and Preserved Left Ventricular Ejection Fraction","volume":"186","author":"Basmadjian","year":"2023","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1136\/hrt.2010.217273","article-title":"Increased thrombin generation and platelet activation are associated with deficiency in high molecular weight multimers of von Willebrand factor in patients with moderate-to-severe aortic stenosis","volume":"97","author":"Natorska","year":"2011","journal-title":"Heart"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCULATIONAHA.115.016757","article-title":"Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve","volume":"132","author":"Bouchareb","year":"2015","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/eurheartj\/ehy696","article-title":"Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis","volume":"40","author":"Bouchareb","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/cvr\/cvx089","article-title":"OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-\u03baB pathway","volume":"113","author":"Nsaibia","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jss.2014.03.051","article-title":"Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation","volume":"190","author":"Venardos","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1161\/01.ATV.0000134298.25489.92","article-title":"Thrombomodulin-protein C-EPCR system: Integrated to regulate coagulation and inflammation","volume":"24","author":"Collen","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2022248118","DOI":"10.1073\/pnas.2022248118","article-title":"Thrombomodulin is essential for maintaining quiescence in vascular endothelial cells","volume":"118","author":"Giri","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.amjcard.2023.08.001","article-title":"Biomarkers as Prognostic Markers for Aortic Stenosis: A Review","volume":"206","author":"Sarkar","year":"2023","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"White, M., Baral, R., Ryding, A., Tsampasian, V., Ravindrarajah, T., Garg, P., Koskinas, K.C., Clark, A., and Vassiliou, V.S. (2021). Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis. Med. Sci., 9.","DOI":"10.3390\/medsci9020029"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.ahj.2011.02.015","article-title":"In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels","volume":"161","author":"Schumm","year":"2011","journal-title":"Am. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yoon, D., Choi, B., Kim, J.E., Kim, E.Y., Chung, S.H., Min, H.J., Sung, Y., Chang, E.J., and Song, J.K. (2024). Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells. BMC Med., 22.","DOI":"10.1186\/s12916-024-03342-x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102327","DOI":"10.1016\/j.jaut.2019.102327","article-title":"Autotaxin and chronic inflammatory diseases","volume":"104","author":"Magkrioti","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1194\/jlr.R046391","article-title":"Autotaxin: Structure-function and signaling","volume":"55","author":"Perrakis","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mathieu, P., and Boulanger, M.C. (2019). Autotaxin and Lipoprotein Metabolism in Calcific Aortic Valve Disease. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00018"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/joim.12519","article-title":"Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease","volume":"280","author":"Nsaibia","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bcp.2019.03.035","article-title":"Targeting the autotaxin\u2013Lysophosphatidic acid receptor axis in cardiovascular diseases","volume":"164","author":"Zhao","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.bbalip.2008.05.008","article-title":"Roles of lysophosphatidic acid in cardiovascular physiology and disease","volume":"1781","author":"Smyth","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Smyth, S.S., Kraemer, M., Yang, L., Van Hoose, P., and Morris, A.J. (2020). Roles for lysophosphatidic acid signaling in vascular development and disease. Biochim. Biophys. Acta-Mol. Cell Biol. Lipids, 1865.","DOI":"10.1016\/j.bbalip.2020.158734"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/cvr\/cvab142","article-title":"Role of oxidative stress in calcific aortic valve disease and its therapeutic implications","volume":"118","author":"Greenberg","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118569","DOI":"10.1016\/j.atherosclerosis.2024.118569","article-title":"Phospholipid-derived lysophospholipids in (patho) physiology","volume":"398","author":"Prabutzki","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jiang, S., Yang, H., and Li, M. (2023). Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512524"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.jtha.2024.01.006","article-title":"Thrombomodulin: A multifunctional receptor modulating the endothelial quiescence","volume":"22","author":"Giri","year":"2024","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s00059-009-3317-3","article-title":"Growth differentiation factor-15: A new biomarker in cardiovascular disease","volume":"34","author":"Kempf","year":"2009","journal-title":"Herz"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1373\/clinchem.2016.255174","article-title":"Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease","volume":"63","author":"Wollert","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/10408363.2019.1615034","article-title":"Growth differentiation factor 15: A novel biomarker with high clinical potential","volume":"56","author":"Desmedt","year":"2019","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fabiani, I., Santoni, T., Angelillis, M., Petricciuolo, S., Colli, A., Pellegrini, G., Mazzei, D., Pugliese, N.R., Petronio, A.S., and De Caterina, R. (2020). Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092998"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/eurheartj\/ehab395","article-title":"2021 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"43","author":"Vahanian","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1161\/CIR.0000000000000932","article-title":"2020 ACC\/AHA Guideline for the Management of Patients with Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"143","author":"Otto","year":"2021","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lancellotti, P., Zamorano, J.Z., Habib, G., and Badano, L. (2016). The EACVI Textbook of Echocardiography, The European Society of Cardiology Textbooks. [2nd ed.].","DOI":"10.1093\/med\/9780198726012.001.0001"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.5603\/KP.a2013.0316","article-title":"Flow-mediated dilatation (FMD) and prevalence of cardiovascular risk factors: The value of FMD assessment in high risk patients is limited","volume":"72","author":"Wieczorek","year":"2014","journal-title":"Kardiol. Pol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:35:22Z","timestamp":1760031322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":35,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104873"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104873","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]}}}