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Review

The Biological Bases of Group 2 Pulmonary Hypertension

1
Department of Cardiology, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain
2
Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
3
Centro de Investigación Biomédica en Red, CIBERCV, Instituto de Salud Carlos III, 28026 Madrid, Spain
4
Facultad de Medicine, Universidad Complutense de Madrid, 28007 Madrid, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 5884; https://doi.org/10.3390/ijms20235884
Received: 7 November 2019 / Revised: 20 November 2019 / Accepted: 21 November 2019 / Published: 23 November 2019
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension 2.0)
Pulmonary hypertension (PH) is a potentially fatal condition with a prevalence of around 1% in the world population and most commonly caused by left heart disease (PH-LHD). Usually, in PH-LHD, the increase of pulmonary pressure is only conditioned by the retrograde transmission of the left atrial pressure. However, in some cases, the long-term retrograde pressure overload may trigger complex and irreversible biomechanical and biological changes in the pulmonary vasculature. This latter clinical entity, designated as combined pre- and post-capillary PH, is associated with very poor outcomes. The underlying mechanisms of this progression are poorly understood, and most of the current knowledge comes from the field of Group 1-PAH. Treatment is also an unsolved issue in patients with PH-LHD. Targeting the molecular pathways that regulate pulmonary hemodynamics and vascular remodeling has provided excellent results in other forms of PH but has a neutral or detrimental result in patients with PH-LHD. Therefore, a deep and comprehensive biological characterization of PH-LHD is essential to improve the diagnostic and prognostic evaluation of patients and, eventually, identify new therapeutic targets. Ongoing research is aimed at identify candidate genes, variants, non-coding RNAs, and other biomarkers with potential diagnostic and therapeutic implications. In this review, we discuss the state-of-the-art cellular, molecular, genetic, and epigenetic mechanisms potentially involved in PH-LHD. Signaling and effective pathways are particularly emphasized, as well as the current knowledge on -omic biomarkers. Our final aim is to provide readers with the biological foundations on which to ground both clinical and pre-clinical research in the field of PH-LHD. View Full-Text
Keywords: pulmonary hypertension group 2; left heart disease; isolated pulmonary hypertension; combined pulmonary hypertension; gene; epigenetics pulmonary hypertension group 2; left heart disease; isolated pulmonary hypertension; combined pulmonary hypertension; gene; epigenetics
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MDPI and ACS Style

Fernández, A.I.; Yotti, R.; González-Mansilla, A.; Mombiela, T.; Gutiérrez-Ibanes, E.; Pérez del Villar, C.; Navas-Tejedor, P.; Chazo, C.; Martínez-Legazpi, P.; Fernández-Avilés, F.; Bermejo, J. The Biological Bases of Group 2 Pulmonary Hypertension. Int. J. Mol. Sci. 2019, 20, 5884. https://doi.org/10.3390/ijms20235884

AMA Style

Fernández AI, Yotti R, González-Mansilla A, Mombiela T, Gutiérrez-Ibanes E, Pérez del Villar C, Navas-Tejedor P, Chazo C, Martínez-Legazpi P, Fernández-Avilés F, Bermejo J. The Biological Bases of Group 2 Pulmonary Hypertension. International Journal of Molecular Sciences. 2019; 20(23):5884. https://doi.org/10.3390/ijms20235884

Chicago/Turabian Style

Fernández, Ana I., Raquel Yotti, Ana González-Mansilla, Teresa Mombiela, Enrique Gutiérrez-Ibanes, Candelas Pérez del Villar, Paula Navas-Tejedor, Christian Chazo, Pablo Martínez-Legazpi, Francisco Fernández-Avilés, and Javier Bermejo. 2019. "The Biological Bases of Group 2 Pulmonary Hypertension" International Journal of Molecular Sciences 20, no. 23: 5884. https://doi.org/10.3390/ijms20235884

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