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Review

Modulating NO–GC Pathway in Pulmonary Arterial Hypertension

by
Anna D’Agostino
1,†,
Lorena Gioia Lanzafame
2,3,†,
Lorena Buono
1,
Giulia Crisci
3,
Roberta D’Assante
3,
Ilaria Leone
1,
Luigi De Vito
3,
Eduardo Bossone
4,
Antonio Cittadini
3,5 and
Alberto Maria Marra
3,5,*
1
IRCCS SYNLAB SDN, Via Emanuele Gianturco 113, 80143 Naples, Italy
2
Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122 Catania, Italy
3
Department of Translational Medical Sciences, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
4
Department of Public Health, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
5
Gender Interdipartimental Institute of Research (GENESIS), “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2024, 25(1), 36; https://doi.org/10.3390/ijms25010036
Submission received: 13 November 2023 / Revised: 10 December 2023 / Accepted: 15 December 2023 / Published: 19 December 2023
(This article belongs to the Special Issue Advances in Research on Pulmonary Hypertension 2.0)
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Abstract

The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play a significant role in the onset and progression of the disease. Indeed, PAH has been associated with pathophysiologic alterations in vascular function. These are often dictated by increased oxidative stress and impaired modulation of the nitric oxide (NO) pathway. NO reduces the uncontrolled proliferation of vascular smooth muscle cells that leads to occlusion of vessels and an increase in pulmonary vascular resistances, which is the mainstay of PAH development. To date, two classes of NO-pathway modulating drugs are approved for the treatment of PAH: the phosphodiesterase-5 inhibitors (PD5i), sildenafil and tadalafil, and the soluble guanylate cyclase activator (sGC), riociguat. Both drugs provide considerable improvement in exercise capacity and pulmonary hemodynamics. PD5i are the recommended drugs for first-line PAH treatment, whereas sGCs are also the only drug approved for the treatment of resistant or inoperable chronic thromboembolic pulmonary hypertension. In this review, we will focus on the current information regarding the nitric oxide pathway and its modulation in PAH.
Keywords: pulmonary arterial hypertension; nitric oxide; riociguat; right ventricle pulmonary arterial hypertension; nitric oxide; riociguat; right ventricle

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MDPI and ACS Style

D’Agostino, A.; Lanzafame, L.G.; Buono, L.; Crisci, G.; D’Assante, R.; Leone, I.; De Vito, L.; Bossone, E.; Cittadini, A.; Marra, A.M. Modulating NO–GC Pathway in Pulmonary Arterial Hypertension. Int. J. Mol. Sci. 2024, 25, 36. https://doi.org/10.3390/ijms25010036

AMA Style

D’Agostino A, Lanzafame LG, Buono L, Crisci G, D’Assante R, Leone I, De Vito L, Bossone E, Cittadini A, Marra AM. Modulating NO–GC Pathway in Pulmonary Arterial Hypertension. International Journal of Molecular Sciences. 2024; 25(1):36. https://doi.org/10.3390/ijms25010036

Chicago/Turabian Style

D’Agostino, Anna, Lorena Gioia Lanzafame, Lorena Buono, Giulia Crisci, Roberta D’Assante, Ilaria Leone, Luigi De Vito, Eduardo Bossone, Antonio Cittadini, and Alberto Maria Marra. 2024. "Modulating NO–GC Pathway in Pulmonary Arterial Hypertension" International Journal of Molecular Sciences 25, no. 1: 36. https://doi.org/10.3390/ijms25010036

APA Style

D’Agostino, A., Lanzafame, L. G., Buono, L., Crisci, G., D’Assante, R., Leone, I., De Vito, L., Bossone, E., Cittadini, A., & Marra, A. M. (2024). Modulating NO–GC Pathway in Pulmonary Arterial Hypertension. International Journal of Molecular Sciences, 25(1), 36. https://doi.org/10.3390/ijms25010036

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