Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging

Figures

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  Figure 1. A diagram representing angiotensin-converting enzyme (ACE) and ACE-secretase. Phospholipid bilayer of the cell membrane (indicated by yellow), ACE-secretase bound to the cell membrane (indicated by red), and ACE (indicated by blue). The figures for ACE depict two major domains, the N- and C-catalytic domains, which are active sites that bind zinc ions. ACE-secretase cleaves at a site nearby the N-catalytic domains to form circulating ACE. This circulating and non-circulating ACE can hydrolyze and cleave angiotensin I to form angiotensin II in the mechanisms described in the text.

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  Figure 2. A schematic diagram of the Renin-Angiotensin System (RAS) pathway and the points in which inhibition may occur. The three key organs of the RAS pathway include the lungs, liver, and kidney. The RAS pathway revolves around the production of angiotensinogen, the precursor to angiotensin originating from the liver. Through renin produced in the kidney, followed by ACE produced in the lungs, angiotensin II can subsequently be formed. By inhibiting either renin or ACE, the progress of the RAS pathway can effectively be halted. Below the schematic is a summary of the final physiological effects followed by the binding of each target is listed at the bottom of the diagram. Angiotensin II will produce vasoconstriction, proliferation, inflammation, and fibrosis through binding to the AT1 receptor (AT1R). Binding to AT2 receptor or MasR, following conversion to Angiotensin-(1-7), will result in opposing physiologic effects. This conversion to Angiotensin-(1-7) is known as alternative RAS activation and is enabled by the angiotensin-converting-enzyme-2 (ACE2) and neprilysin (NEP), a protease abundantly found in the kidneys.