{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:02:24Z","timestamp":1779840144441,"version":"3.53.1"},"reference-count":46,"publisher":"Georg Thieme Verlag KG","funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["2022ZXM5AF"],"award-info":[{"award-number":["2022ZXM5AF"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:p>The proline-rich tyrosine kinase Pyk2 is highly expressed in platelets, where it regulates platelet activation, primary hemostasis, and arterial and venous thrombosis. Recently a role for Pyk2 in acute lung injury and polymicrobial sepsis has been demonstrated. In this study we have investigated the contribution of Pyk2 in platelet activation and microvascular thrombosis in a murine model of low-grade endotoxemia.<\/jats:p>\n                  <jats:p>Endotoxemia was induced by injection of 0.5\u2009mg\/kg LPS in wild-type (WT) and Pyk2 knockout (KO) mice and disease state, platelet activation, platelet\u2013leukocyte aggregates, and microvascular thrombosis were analyzed after 4\u2009hours.<\/jats:p>\n                  <jats:p>We found that the severity of endotoxemia was significantly lower in Pyk2 KO mice compared with WT littermates. Moreover, histological analysis of lungs and liver explanted from LPS-injected animals revealed that the number of vessels occluded by thrombi was significantly reduced in the absence of Pyk2. Ex vivo experiments demonstrated that injection of LPS sensitized circulating platelets from WT animals to TRAP4-induced aggregation. This effect involved Toll-like receptor 4 and was almost completely suppressed in Pyk2 KO mice. Potentiation of TRAP4-induced PI3K and MAPK induced by LPS in WT platelets was also completely lost in Pyk2-deficient platelets. Finally, in whole blood from Pyk2 KO mice platelet\u2013leukocyte aggregates was significantly lower compared with WT littermates and the ability of TRAP4-stimulated Pyk2-deficient platelets to recruit neutrophils was compromised as well.<\/jats:p>\n                  <jats:p>This study demonstrates a novel role for Pyk2 in LPS-induced endotoxemia and suggests that targeting Pyk2 may be beneficial in the treatment of vascular complications associated with systemic inflammation.<\/jats:p>","DOI":"10.1055\/a-2876-1250","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:49:11Z","timestamp":1779144551000},"source":"Crossref","is-referenced-by-count":0,"title":["The Proline-Rich Tyrosine Kinase Pyk2 Regulates Platelet Activation and Microvascular Thrombosis in a Model of Low-Grade Endotoxemia"],"prefix":"10.1055","author":[{"given":"Michela","family":"Gemme","sequence":"first","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Galgano","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Pennsylvania, United States","place":["Pittsburgh"],"department":["Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Rustichelli","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]},{"name":"University School for Advanced Studies Pavia, Italy","place":["Pavia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Giuseppina","family":"Di Pasqua","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Internal Medicine and Therapeutics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zar\u00e0","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Campomilla","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Monti","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni Francesco","family":"Guidetti","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ferrigno","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Internal Medicine and Therapeutics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Torti","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Canobbio","sequence":"additional","affiliation":[{"name":"University of Pavia, Lombardia, Italy","place":["Pavia"],"department":["Department of Biology and Biotechnology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"863846","DOI":"10.3389\/fcvm.2022.863846","article-title":"Implication of platelets in immuno-thrombosis and thrombo-inflammation","volume":"9","author":"Y Zaid","year":"2022","journal-title":"Front Cardiovasc Med"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"7462","DOI":"10.3390\/ijms24087462","article-title":"Blood platelets in infection: the multiple roles of the platelet signalling machinery","volume":"24","author":"S MG Trivigno","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1161\/ATVBAHA.124.320149","article-title":"Thromboinflammation and the role of platelets","volume":"44","author":"A Mack","year":"2024","journal-title":"Arterioscler Thromb Vasc 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