期刊
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
卷 25, 期 5, 页码 384-395出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNH.0000000000000254
关键词
angiotensin converting enzyme 2 activation; cardiovascular disease; diminazene aceturate; hypertension; renin-angiotensin system
资金
- National Health and Medical Research Council of Australia (NHMRC)
- Diabetes Australia
- Austin Medical Research Foundation
Purpose of reviewAngiotensin converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system through actions to degrade angiotensin II. Loss of ACE2 can contribute to the development and progression of cardiovascular disease, and experimental studies have highlighted a beneficial role for novel therapeutic approaches that activate or replenish tissue ACE2. This review focuses on experimental studies that have used the off-target effects of the antitrypanosomal agent, diminazene aceturate (DIZE) to activate ACE2.Recent findingsIn cardiovascular disease, activation of the classical renin-angiotensin system and depletion of ACE2 leads to pathophysiological changes. One approach to activate ACE2 involves the drug DIZE, which has been shown to have beneficial effects in experimental models of hypertension, pulmonary hypertension, myocardial infarction, stroke, atherosclerosis, type 1 diabetes, and eye disease. The precise mechanism of action of DIZE to activate ACE2 remains under scrutiny.SummaryActivation of ACE2 may represent an important therapeutic approach in cardiovascular disease. To date, most studies have focused on the off-target actions of DIZE, in experimental models of disease. More research is required to determine the exact mechanism of action of DIZE and evaluate its therapeutic potential in comparison with currently available clinical interventions. There are no clinical studies of DIZE, and its side-effects, and toxicity make such studies unlikely. Hence, new methods of selectively activating or replenishing ACE2 will be needed in the future if this approach is to be used in a clinical context.
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