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. 2015 Jul 31;47(7):e175. doi: 10.1038/emm.2015.45

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Copyright © 2015 KSBMB.

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Proposed multifactorial pathogenesis of pulmonary arterial hypertension (PAH). This figure presents the complex nature of heritable PAH (HPAH) and idiopathic PAH (IPAH). In the case of HPAH, the major driver ‘primary hit' maybe genetic mutation of HPA-associated genes. In many PAH patients, unknown or undetectable ‘secondary hit' mechanisms such as epigenetic alteration, gender and other cardiovascular anomalies, as well as environmental factors, might cooperate in the progression of HPAH. Commonly, IPAH is caused by the combination effect of multiple cues such as non-heritable genetic or epigenetic variations, as well as environmental statuses.