Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies
Abstract
:1. Introduction
2. ACE2 Signaling in PAH Pathophysiology—Molecular Mechanisms
3. Clinical Relevance of ACE2 Signaling in PAH—Potential as Therapeutic Target
4. Concluding Remarks—Challenges and Opportunities
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Effect | ACE2 Signaling-Dependent Molecular Mechanism | References |
---|---|---|
↓SMC proliferation and migration in PA | ERK1/2 and JAK/STAT3 signaling inhibition | [22] |
↓Inflammation and oxidative stress | ↓mRNA levels of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and NADPH subunit (gp91phox), ↑anti-inflammatory cytokine IL-10 | [21] |
↓Fibrosis | ↓mRNA levels of TGF-β and collagen fiber production | [21] |
↑NO | ACE2-mediated phosphorylation (Ser1177) and dephosphorylation (Thr495) of endothelial nitric oxide synthetase | [24] |
Cardiomyocyte hypertrophy inhibition | Ang-(1-7)-induced upregulation of a nitric oxide/guanosine 3′,5′-cyclic monophosphate-dependent pathway | [25] |
Pulmonary vascular remodeling suppression | ↑Apoptosis via Hippo signaling | [26] |
↑PASMC proliferation and migration | ↓ACE2 expression via HIF-1-dependent upregulation of microRNA let-7b | [29] |
↑PASMC apoptosis | ↓FAK signaling and ↑pro-apoptotic caspase-3 | [30] |
↑ACE2 protein stability and ↑Ang-(1-7) and NO levels | AMPK-related ACE2 phosphorylation at Ser680 | [31] |
↑ACE2 protein degradation | MDM2-mediated ACE2 ubiquitination at K788 | [32] |
↓ACE2 protein levels and activity | Autoantibodies against ACE2 | [33,34] |
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Papavassiliou, K.A.; Gogou, V.A.; Papavassiliou, A.G. Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies. Int. J. Mol. Sci. 2023, 24, 17441. https://doi.org/10.3390/ijms242417441
Papavassiliou KA, Gogou VA, Papavassiliou AG. Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies. International Journal of Molecular Sciences. 2023; 24(24):17441. https://doi.org/10.3390/ijms242417441
Chicago/Turabian StylePapavassiliou, Kostas A., Vassiliki A. Gogou, and Athanasios G. Papavassiliou. 2023. "Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies" International Journal of Molecular Sciences 24, no. 24: 17441. https://doi.org/10.3390/ijms242417441