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Review
. 2012 Dec;122(12):4306-13.
doi: 10.1172/JCI60658. Epub 2012 Dec 3.

Molecular pathogenesis of pulmonary arterial hypertension

Marlene Rabinovitch  1
Affiliations
Review

Molecular pathogenesis of pulmonary arterial hypertension

Marlene Rabinovitch. J Clin Invest. 2012 Dec.

Abstract

Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH--together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function--have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways.

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Figures

Figure 1
Figure 1. Vascular abnormalities associated with PAH.
This schema depicts the abnormalities throughout the pulmonary circulation: abnormal muscularization of distal and medial precapillary arteries, loss of precapillary arteries, thickening of large PAs, and neointimal formation that is particularly occlusive in vessels less than 500–100 μM and in plexiform lesions therein.
Figure 2
Figure 2. Factors that converge in the molecular pathogenesis of PAH.
This schema focuses on the interactions among inflammation, altered cellular metabolism, and genetic/epigenetic abnormalities in the pathogenesis of PAH.
See this image and copyright information in PMC

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References

    1. Simonneau G, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 suppl):S43–S54. doi: 10.1016/j.jacc.2009.04.012. - DOI - PubMed
    1. Rabinovitch M, et al. Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension: A correlation of light with scanning electron microscopy and transmission electron microscopy. Lab Invest. 1986;55(6):632–653. - PubMed
    1. Rosenberg HC, Rabinovitch M. Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension. Am J Physiol. 1988;255(6 pt 2):H1484–H1491. - PubMed
    1. Dewachter L, et al. Angiopoietin/Tie2 pathway influences smooth muscle hyperplasia in idiopathic pulmonary hypertension. Am J Respir Crit Care Med. 2006;174(9):1025–1033. doi: 10.1164/rccm.200602-304OC. - DOI - PubMed
    1. Thompson K, Rabinovitch M. Exogenous leukocyte and endogenous elastases can mediate mitogenic activity in pulmonary artery smooth muscle cells by release of extracellular-matrix bound basic fibroblast growth factor. J Cell Physiol. 1996;166(3):495–505. doi: 10.1002/(SICI)1097-4652(199603)166:3<495::AID-JCP4>3.0.CO;2-K. - DOI - PubMed

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