Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies

Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has adva...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-12, Vol.24 (24), p.17441
Main Authors: Papavassiliou, Kostas A, Gogou, Vassiliki A, Papavassiliou, Athanasios G
Format: Article
Language:English
Subjects:
Angiotensin I - metabolism
angiotensin-(1-7)
angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - therapeutic use
Apoptosis
Connective tissue
Cytokines
Disease
DNA methylation
Enzymes
Familial Primary Pulmonary Hypertension
Heart failure
Humans
Hypertension, Pulmonary - drug therapy
Hypoxia
Inflammation
Kinases
Medical prognosis
MicroRNAs
Nitric oxide
Oxidative stress
Pathophysiology
Peptide Fragments - metabolism
Peptidyl-Dipeptidase A - metabolism
Phosphorylation
Pneumonectomy
Proteins
Pulmonary Arterial Hypertension
Pulmonary arteries
Pulmonary hypertension
Receptors, G-Protein-Coupled - metabolism
Renin-Angiotensin System
Smooth muscle
Veins & arteries
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Summary:Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242417441