{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:07:03Z","timestamp":1780344423256,"version":"3.54.1"},"reference-count":120,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gutenberg Research Foundation","award":["CVON2014-09"],"award-info":[{"award-number":["CVON2014-09"]}]},{"name":"The Netherlands Heart Foundation","award":["CVON2014-09"],"award-info":[{"award-number":["CVON2014-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, is underdiagnosed in the general population. Despite the extensive research performed to unravel its pathophysiology, inadequate knowledge exists, thus preventing the development of new treatments. This review aims to highlight the essential elements of atherosclerosis contributing to the pathophysiology of PAD. Furthermore, emphasis will be placed on the role of thrombo-inflammation, with particular focus on platelet and coagulation activation as well as cell\u2013cell interactions. Additional insight will be then discussed to reveal the contribution of hypercoagulability to the development of vascular diseases such as PAD. Lastly, the current antithrombotic treatments will be discussed, and light will be shed on promising new targets aiming to aid the development of new treatments.<\/jats:p>","DOI":"10.3390\/ph15111428","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T06:02:29Z","timestamp":1668751349000},"page":"1428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Integrating Mechanisms in Thrombotic Peripheral Arterial Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Magdolna","family":"Nagy","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-2583","authenticated-orcid":false,"given":"Paola E. J.","family":"van der Meijden","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Glunz","sequence":"additional","affiliation":[{"name":"Cardiovascular Research, Bayer AG, 42117 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7867-6957","authenticated-orcid":false,"given":"Leon","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Lutgens","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 10785 Munich, Germany"},{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian\u2019s University, 80539 Munich, Germany"},{"name":"Experimental Cardiovascular Immunology Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-4463","authenticated-orcid":false,"given":"Hugo","family":"ten Cate","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Internal Medicine, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"},{"name":"Center for Thrombosis and Hemostasis, Gutenberg University Mainz, 55122 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2108-8286","authenticated-orcid":false,"given":"Stefan","family":"Heitmeier","sequence":"additional","affiliation":[{"name":"Cardiovascular Research, Bayer AG, 42117 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-334X","authenticated-orcid":false,"given":"Henri M. H.","family":"Spronk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Internal Medicine, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"TASC II Working Group Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)","volume":"45","author":"Norgren","year":"2007","journal-title":"J. Vasc. 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