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Borek et al. Rare Dis Orphan Drugs J 2023;2:5 Rare Disease and
DOI: 10.20517/rdodj.2022.20
Orphan Drugs Journal

Review Open Access

Immune cell-derived serine protease as pathogenic
drivers of vascular remodeling in pulmonary arterial

hypertension

1
Izabela Borek , Grazyna Kwapiszewska 1,2,3
1
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria.
2
Otto Loewi Research Center, Medical University of Graz, Graz 8010, Austria.
3
Institute for Lung Health, Giessen 35392, Germany.
Correspondence to: Prof. Grazyna Kwapiszewska, Otto Loewi Research Center, Medical University of Graz, Graz 8010, Austria.
E-mail: grazyna.kwapiszewska@lvr.lbg.ac.at
How to cite this article: Borek I, Kwapiszewska G. Immune cell-derived serine protease as pathogenic drivers of vascular
remodeling in pulmonary arterial hypertension. Rare Dis Orphan Drugs J 2023;2:5. https://dx.doi.org/10.20517/rdodj.2022.20
Received: 16 Oct 2022 First Decision: 6 Feb 2023 Revised: 27 Feb 2023 Accepted: 9 Mar 2023 Published: 22 Mar 2023

Academic Editor: Daniel Scherman, Brice Korkmaz Copy Editor: Ying Han Production Editor: Ying Han

Abstract
In recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong
underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of
pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the
vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been
shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are
involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of
bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have
devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-
inflammatory role of serine proteases in vascular pathology observed in the context of this disease.

Keywords: Pulmonary arterial hypertension, serine proteases, pulmonary arterial remodeling, inflammation, mast
cells, neutrophils

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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