Neuroserpin, a thrombolytic serine protease inhibitor (serpin), blocks transplant vasculopathy with associated modification of T-helper cell subsets.

Thrombosis and Haemostasis
G Munuswamy-RamanujamAlexandra Lucas

Abstract

Thrombolytic serine proteases not only initiate fibrinolysis, but also are up-regulated in vascular disease and acute inflammatory responses. Although the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) is considered a main regulator of thrombolysis, PAI-1 is also associated with vascular inflammation. The role of other serpins that target thrombolytic proteases, PAI-2, PAI-3, and neuroserpin (NSP), in vascular inflammation is, however, less well defined. NSP is a mammalian serpin that, similar to PAI-1, inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA, respectively) and has been most closely associated with the nervous system, with a demonstrated protective role after cerebral infarction in mouse models. However, the role of NSP in systemic arterial inflammation and plaque growth is not known. Serp-1 is a myxoma viral serpin that also inhibits tPA and uPA, as well as additionally inhibiting plasmin and factor Xa (fXa). Serp-1 has proven highly potent anti-inflammatory and anti-atherogenic activity. Here we assess the effects of NSP treatment on plaque growth and T-helper (Th) lymphocyte activity in a mouse aortic allograft transplant model, with comparison to Serp-1. NSP and ...Continue Reading

Citations

Jun 11, 2011·Veterinary Research·Bart SpiesschaertGerlinde R Van de Walle
Sep 19, 2016·Seminars in Cell & Developmental Biology·Tet Woo LeeNigel P Birch
Dec 2, 2015·The Journal of Biological Chemistry·Sriram AmbadapadiAlexandra Lucas
May 24, 2017·Frontiers in Cellular Neuroscience·Lancelot J MillarZoltán Molnár
Apr 5, 2020·Journal of Clinical Medicine·Jordan R YaronAlexandra R Lucas
Mar 7, 2021·International Journal of Molecular Sciences·Srinu TumparaSabina Janciauskiene
Apr 20, 2021·Frontiers in Cardiovascular Medicine·Jordan R YaronAlexandra R Lucas
Aug 19, 2021·Cellular and Molecular Life Sciences : CMLS·Emanuela D'AcuntoElena Miranda

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