Abstract
A 2018 report from the American Heart Association 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, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two 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 hydrolyzes beta-amyloid, reducing 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 AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events.
Highlights
angiotensin-converting enzyme (ACE) plays a major role in the angiotensin–renin system that regulates blood pressure and salt balance
ACE inhibitors can be used as treatment options for hypertension and other health conditions, while alterations of the ACE gene are associated with Alzheimer’s disease (AD)
First-line medications include ACE inhibitors that have been well established in medicine
Summary
ACE plays a major role in the angiotensin–renin system that regulates blood pressure and salt balance. ACE inhibitors had been initially reported as a medication to treat hypertension [3,4]. The ACE gene encodes a protein with 732 amino acid residues and a molecular weight of 80,073 [6]. It is an important target for the treatment of hypertension. Essential hypertension, is the condition of having high blood pressure. Secondary hypertension is high blood pressure caused by another medical condition. ACE inhibitors are well-established medications for hypertension, which is a major risk of cognitive impairment and dementia [14] and of death by COVID-19 [15]. We hope to provide the links between ACE and hypertension, AD, neurological diseases, and aging
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