Angiotensin 2 converting enzyme
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These studies suggest that ACE2 plays a crucial role in cardiovascular and renal health by converting angiotensin II to angiotensin (1-7), with potential therapeutic applications in diseases like hypertension, diabetic kidney disease, and cardiovascular disease, while also being involved in COVID-19 pathogenesis.
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Angiotensin-Converting Enzyme 2 (ACE2): Key Insights and Therapeutic Potential
Introduction to Angiotensin-Converting Enzyme 2 (ACE2)
Angiotensin-converting enzyme 2 (ACE2) is a critical enzyme in the renin-angiotensin system (RAS), which plays a significant role in regulating cardiovascular and renal functions. ACE2 converts angiotensin II (Ang II) into angiotensin-(1-7) [Ang-(1-7)], a peptide with vasodilatory and anti-inflammatory properties, counterbalancing the effects of Ang II .
ACE2 and Angiotensin II Conversion
Role of ACE2 in Angiotensin II Degradation
ACE2 efficiently degrades Ang II, leading to the formation of Ang-(1-7). This conversion is crucial as Ang-(1-7) exerts effects opposite to those of Ang II, including vasodilation and anti-proliferation . In diabetic nephropathy, decreased ACE2 expression in the kidneys correlates with increased Ang II levels, contributing to glomerular injury and albuminuria. Enhancing ACE2 activity has shown potential in mitigating these effects.
Alternative Pathways for Angiotensin-(1-7) Formation
While ACE2 is a primary enzyme for converting Ang II to Ang-(1-7), other enzymes like prolyloligopeptidase (POP) also contribute to this process. Studies have shown that in the absence of ACE2, POP can still facilitate Ang-(1-7) formation, particularly in the circulation and lungs, though not in the kidneys where ACE2 is more critical.
Therapeutic Potential of ACE2
Recombinant ACE2 Administration
Recombinant human ACE2 (rhACE2) has been explored as a therapeutic agent. In clinical studies, rhACE2 administration resulted in a dose-dependent decrease in Ang II levels and an increase in Ang-(1-7), without significant cardiovascular side effects, suggesting its potential for treating conditions with elevated Ang II.
ACE2 in Cardiovascular and Renal Diseases
ACE2 deficiency is linked to elevated Ang II levels, leading to hypertension, left ventricular hypertrophy, and progressive renal damage. Interventions that replenish or enhance ACE2 activity have shown promise in reducing these adverse effects, highlighting ACE2's therapeutic potential in cardiovascular and renal diseases .
ACE2 and Diabetic Cardiomyopathy
In diabetic cardiomyopathy models, ACE2 overexpression has been shown to inhibit myocardial collagen accumulation, improve left ventricular function, and reduce fibrosis. These findings suggest that ACE2 could be a valuable therapeutic target for managing diabetic cardiomyopathy.
ACE2 and COVID-19
ACE2 as a SARS-CoV-2 Receptor
ACE2 is the functional receptor for SARS-CoV-2, the virus responsible for COVID-19. The widespread expression of ACE2 in various tissues explains the multi-organ impact of the virus. Understanding ACE2's role in COVID-19 pathophysiology is crucial for developing effective treatments.
Impact of RAS Inhibitors on ACE2 Expression
Concerns have been raised about the potential for RAS inhibitors (RASIs) to increase ACE2 expression, potentially exacerbating COVID-19. However, systematic reviews of animal studies indicate that ACE2 overexpression due to RASI treatment is rare, suggesting that these medications may not significantly impact COVID-19 severity.
Conclusion
ACE2 plays a pivotal role in the RAS by converting Ang II to Ang-(1-7), thus mitigating the harmful effects of Ang II. Its therapeutic potential is evident in various cardiovascular and renal diseases, as well as in the context of COVID-19. Ongoing research into ACE2 modulation and its implications for disease treatment continues to be of paramount importance.
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