Pathophysiologic and therapeutic importance of tissue ACE: a consensus report.
Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contribute to cardiovascular disease through direct pathological tissue effects, including vascular remodeling and inflammation, as well as indirect action on nitric oxide bioavailability and its consequences. The endothelium plays a pivotal role in both vascular function and structure; thus, the predominant localization of ACE to the endothelium has implications for the pathobiology of vascular disease, such as coronary artery disease. Numerous experimental studies and clinical trials support the emerging realization that tissue ACE is a vital therapeutic target, and that its inhibition may restore endothelial function or prevent endothelial dysfunction. These effects exceed those attributable to blood pressure reduction alone; hence, ACE inhibitors may exert an important part of their effects through direct tissue action. Pharmacologic studies show that while ACE inhibitors may differ according to their binding affinity for tissue ACE the clinical significance remains to be determined.
Dzau
Victor J
VJ
Department of Medicine, Brigham Women's Hospital, Boston, MA 02115, USA. VDZAU@partners.org
Bernstein
Kenneth
K
Celermajer
David
D
Cohen
Jerome
J
Dahlöf
Björn
B
Deanfield
John
J
Diez
Javier
J
Drexler
Helmut
H
Ferrari
Roberto
R
Van Gilst
Wiek
W
Hansson
Lennart
L
Hornig
Burkhard
B
Husain
Ahsan
A
Johnston
Colin
C
Lazar
Harold
H
Lonn
Eva
E
Lüscher
Thomas
T
Mancini
John
J
Mimran
Albert
A
Pepine
Carl
C
Rabelink
Ton
T
Remme
Willem
W
Ruilope
Luis
L
Ruzicka
Marcel
M
Schunkert
Heribert
H
Swedberg
Karl
K
Unger
Thomas
T
Vaughan
Douglas
D
Weber
Michael
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001682:Biological Availability; D001920:Bradykinin / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D053818:Chymases; D002986:Clinical Trials as Topic; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D001920:Bradykinin