The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data

Victor J. Dzau*, Kenneth Bernstein, David Celermajer, Jerome Cohen, Björn Dahlöf, John Deanfield, Javier Diez, Helmut Drexler, Roberto Ferrari, Wiek Van Gilst, Lennart Hansson, Burkhard Hornig, Ahsan Husain, Colin Johnston, Harold Lazar, Eva Lonn, Thomas Lüscher, John Mancini, Albert Mimran, Carl PepineTon Rabelink, Willem Remme, Luis Ruilope, Marcel Ruzicka, Heribert Schunkert, Karl Swedberg, Thomas Unger, Douglas Vaughan, Michael Weber

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

212 Scopus citations


Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Original languageEnglish (US)
Pages (from-to)1-20
Number of pages20
JournalAmerican Journal of Cardiology
Issue number9 SUPPL. 1
StatePublished - Nov 9 2001

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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