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Pathophysiologic and therapeutic importance of tissue ACE: a consensus report
Victor J Dzau1, Kenneth Bernstein, David Celermajer
1Department of Medicine, Brigham Women's Hospital, Boston, MA 02115, USA. VDZAU@partners.org
Cardiovascular Drugs and Therapy
|July 2, 2002
Summary
Angiotensin-converting enzyme (ACE) activation drives cardiovascular disease. Inhibiting tissue ACE may restore endothelial function beyond blood pressure reduction, offering a key therapeutic strategy.
Area of Science:
- Cardiovascular Science
- Endothelial Biology
- Pharmacology
Background:
- Angiotensin-converting enzyme (ACE) activation and angiotensin II production contribute to cardiovascular disease via direct tissue effects and altered nitric oxide bioavailability.
- The endothelium's central role in vascular health is significant, with ACE predominantly localized there, impacting vascular disease pathobiology like coronary artery disease.
Purpose of the Study:
- To highlight tissue ACE as a critical therapeutic target in cardiovascular disease.
- To explore the potential of ACE inhibition in restoring or preventing endothelial dysfunction.
- To investigate whether ACE inhibitor effects extend beyond blood pressure reduction through direct tissue actions.
Main Methods:
- Review of experimental studies and clinical trials on tissue ACE inhibition.
- Pharmacological analysis of ACE inhibitors' binding affinities for tissue ACE.
Main Results:
- Evidence suggests tissue ACE inhibition can restore endothelial function, independent of blood pressure reduction.
- Direct tissue actions of ACE inhibitors appear to contribute significantly to their therapeutic effects.
Conclusions:
- Tissue ACE is a vital therapeutic target for cardiovascular diseases.
- ACE inhibitors may offer direct benefits to endothelial function, exceeding their antihypertensive effects.
- Further research is needed to determine the clinical significance of varying ACE inhibitor binding affinities for tissue ACE.