Angio convert enzyme
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Angiotensin-Converting Enzyme (ACE) and ACE2: Key Players in the Renin-Angiotensin System
Introduction to Angiotensin-Converting Enzyme (ACE)
Angiotensin-converting enzyme (ACE) is a critical component of the renin-angiotensin system (RAS), which regulates blood pressure and fluid balance. ACE primarily converts angiotensin I to the potent vasoconstrictor angiotensin II and inactivates bradykinin, a vasodilator . This dual function makes ACE a significant target in managing hypertension and cardiovascular diseases.
Discovery and Function of ACE2
ACE2, a homologue of ACE, was identified from a human heart failure ventricle cDNA library. Unlike ACE, which is widely distributed, ACE2 is predominantly expressed in the heart, kidney, and testis. ACE2 converts angiotensin I to angiotensin 1-9, which is further processed to angiotensin-(1-7) by ACE. Angiotensin-(1-7) exerts effects opposite to those of angiotensin II, promoting vasodilation and anti-proliferative actions .
Structural and Functional Differences Between ACE and ACE2
The catalytic mechanisms of ACE and ACE2 are similar, but structural differences in their active sites account for their distinct substrate specificities. ACE functions as a dipeptidyl carboxypeptidase, while ACE2 acts as a monocarboxypeptidase. These differences explain why classical ACE inhibitors, such as lisinopril, do not inhibit ACE2. ACE2's ability to cleave a variety of peptides, including angiotensin II, highlights its unique role in the RAS.
ACE2 in Cardiovascular and Renal Systems
ACE2 plays a crucial role in the cardiovascular and renal systems by counterbalancing the effects of ACE. It degrades angiotensin II, reducing its harmful effects on the heart and kidneys. In diabetic nephropathy, decreased ACE2 expression correlates with increased glomerular injury, suggesting that enhancing ACE2 activity could be a therapeutic strategy. Overexpression of ACE2 has been shown to improve left ventricular remodeling and function in diabetic cardiomyopathy, indicating its potential in treating heart diseases.
ACE2 and Integrin Signaling
Recent studies have revealed that both ACE and ACE2 can bind integrin subunits, influencing cell adhesion and signaling. Soluble ACE2 (sACE2) can suppress integrin signaling mediated by focal adhesion kinase (FAK) and increase the expression of Akt, a key signaling molecule. This suggests that ACE2 may play a role in modulating cell-extracellular matrix interactions and cell survival, which could be important in pathological cardiac remodeling.
ACE2 in the Context of COVID-19
ACE2 has gained significant attention as the receptor for the novel coronavirus SARS-CoV-2, which causes COVID-19. Despite its role in viral entry, ACE2's protective functions in the lungs and cardiovascular system make it a paradoxical but potential therapeutic target. Enhancing ACE2 activity could mitigate cardiopulmonary diseases, including those exacerbated by COVID-19.
Conclusion
ACE and ACE2 are pivotal enzymes in the RAS, with ACE promoting vasoconstriction and ACE2 facilitating vasodilation and cardioprotection. Understanding their distinct roles and interactions opens avenues for targeted therapies in cardiovascular and renal diseases, as well as potential treatments for conditions like COVID-19. The balance between ACE and ACE2 activities is crucial for maintaining cardiovascular health and managing disease states.
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