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Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging
Version 1
: Received: 10 October 2021 / Approved: 13 October 2021 / Online: 13 October 2021 (11:04:43 CEST)
A peer-reviewed article of this Preprint also exists.
Le, D.; Brown, L.; Malik, K.; Murakami, S. Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging. Int. J. Mol. Sci. 2021, 22, 13178. Le, D.; Brown, L.; Malik, K.; Murakami, S. Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging. Int. J. Mol. Sci. 2021, 22, 13178.
Journal reference: Int. J. Mol. Sci. 2021, 22, 13178
DOI: 10.3390/ijms222413178
Abstract
A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.
Keywords
AGING; Age-related comorbidities; Angiotensin-Converting Enzyme; Amyloid-degrading enzyme; Alzheimer’s disease; Dementia; Hypertension; Life extension; Stress resistance
Subject
MEDICINE & PHARMACOLOGY, Cardiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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