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• W1961615251 abstract "Abstract Vascular remodelling is a hallmark of pulmonary hypertension ( PH ) and is characterized by enhanced proliferation of pulmonary artery smooth muscle cells ( PASMCs ). Accumulating evidence indicates a crucial role of transcription factors in the vascular remodelling processes. Here, we characterize the involvement of meprin β , a novel activator protein‐1 ( AP ‐1) effector molecule, in PH . Fra‐2 transgenic ( TG ) mice exhibited increased right ventricular systolic pressure ( RVSP ), accompanied by vascular remodelling and activation of the pro‐proliferative and pro‐fibrotic AKT pathway. Microarray studies revealed the collagen‐processing metalloprotease meprin β as the most up‐regulated gene in Fra‐2 TG mice. Its expression, increased at all investigated time points, preceded the decreased expression of MMPs and increased TGF β , followed by collagen deposition. Correspondingly, remodelled pulmonary arteries from explanted idiopathic pulmonary arterial hypertension ( IPAH ) patients' lungs exhibited pronounced expression of meprin β . Fra‐2 and meprin β expression in human PASMCs was regulated by PDGF‐BB and TGF β in a complementary fashion. Importantly, PDGF‐BB ‐dependent proliferation was attenuated by silencing AP ‐1 expression or by meprin β inhibition. This study delineates a novel molecular mechanism underlying PASMCs proliferation and extracellular matrix ( ECM ) deposition by identifying meprin β as an important mediator in regulating vascular remodelling processes. Thus, meprin β may represent a new molecule that can be targeted in pulmonary hypertension. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd." @default.
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• W1961615251 date "2014-01-31" @default.
• W1961615251 modified "2023-10-03" @default.
• W1961615251 title "Meprin <i>β</i>, a novel mediator of vascular remodelling underlying pulmonary hypertension" @default.
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• W1961615251 doi "https://doi.org/10.1002/path.4303" @default.
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