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Vascular remodeling in pulmonary hypertension

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Abstract

Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions, and the appearance of cells expressing smooth muscle-specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular transdifferentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase, and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting.

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Acknowledgments

The authors are supported by grants from the National Institutes of Health (HL073589, HL096982, HL114902, and HL67191).

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  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, 5501 Hopkins Bayview Circle, JHAAC 4A.52, Baltimore, MD, 21224, USA

    Larissa A. Shimoda & Steven S. Laurie

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  1. Larissa A. Shimoda
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Correspondence to Larissa A. Shimoda.

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Shimoda, L.A., Laurie, S.S. Vascular remodeling in pulmonary hypertension. J Mol Med 91, 297–309 (2013). https://doi.org/10.1007/s00109-013-0998-0

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