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Accumulating evidence indicates a crucial role of transcription factors in the vascular remodelling processes. Here, we characterize the involvement of meprin <jats:italic>\u03b2<\/jats:italic>, a novel activator protein\u20101 (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101) effector molecule, in <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>. <jats:italic>Fra\u20102<\/jats:italic> transgenic (<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>) mice exhibited increased right ventricular systolic pressure (<jats:styled-content style=\"fixed-case\">RVSP<\/jats:styled-content>), accompanied by vascular remodelling and activation of the pro\u2010proliferative and pro\u2010fibrotic <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> pathway. Microarray studies revealed the collagen\u2010processing metalloprotease meprin <jats:italic>\u03b2<\/jats:italic> as the most up\u2010regulated gene in <jats:italic>Fra\u20102<\/jats:italic> <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice. Its expression, increased at all investigated time points, preceded the decreased expression of <jats:styled-content style=\"fixed-case\">MMPs<\/jats:styled-content> and increased <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>, followed by collagen deposition. Correspondingly, remodelled pulmonary arteries from explanted idiopathic pulmonary arterial hypertension (<jats:styled-content style=\"fixed-case\">IPAH<\/jats:styled-content>) patients' lungs exhibited pronounced expression of meprin <jats:italic>\u03b2<\/jats:italic>. Fra\u20102 and meprin <jats:italic>\u03b2<\/jats:italic> expression in human <jats:styled-content style=\"fixed-case\">PASMCs<\/jats:styled-content> was regulated by <jats:styled-content style=\"fixed-case\">PDGF\u2010BB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic> in a complementary fashion. Importantly, <jats:styled-content style=\"fixed-case\">PDGF\u2010BB<\/jats:styled-content>\u2010dependent proliferation was attenuated by silencing <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 expression or by meprin <jats:italic>\u03b2<\/jats:italic> inhibition. This study delineates a novel molecular mechanism underlying <jats:styled-content style=\"fixed-case\">PASMCs<\/jats:styled-content> proliferation and extracellular matrix (<jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content>) deposition by identifying meprin <jats:italic>\u03b2<\/jats:italic> as an important mediator in regulating vascular remodelling processes. Thus, meprin <jats:italic>\u03b2<\/jats:italic> may represent a new molecule that can be targeted in pulmonary hypertension. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4303","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T14:05:08Z","timestamp":1384956308000},"page":"7-17","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Meprin <i>\u03b2<\/i>, a novel mediator of vascular remodelling underlying pulmonary hypertension"],"prefix":"10.1002","volume":"233","author":[{"given":"Valentina","family":"Biasin","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh M","family":"Marsh","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research Graz 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