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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:892.)
© 2004 American Heart Association, Inc.

Vascular Biology

Tissue Angiotensin-Converting Enzyme in Imposed and Physiological Flow-Related Arterial Remodeling in Mice

Rob H.P. Hilgers; Paul M.H. Schiffers; Wendy M. Aartsen; Gregorio E. Fazzi; Jos F.M. Smits; Jo G.R. De Mey

From the Department of Pharmacology & Toxicology (R.H.P.H, P.M.H.S., W.M.A., G.E.F., J.F.M.S, J.G.R.D.M.), Cardiovascular Research Institute Maastricht (CARIM), Universiteit Maastricht, Maastricht, the Netherlands; and the School of Life Sciences (G.E.F., J.G.R.D.M.), Transnational University of Limburg, Maastricht, the Netherlands.

Correspondence to Dr Jo G.R. De Mey, Department Pharmacology & Toxicology, CARIM, Universiteit Maastricht, 6200 MD Maastricht, PO Box 616, the Netherlands. E-mail j.demey{at}farmaco.unimaas.nl

Objective— To test whether membrane-bound angiotensin I-converting enzyme (t-ACE) is involved in arterial remodeling, we applied unilateral carotid artery (CA) ligation and studied uterine arteries (UA) before, during, and after pregnancy in t-ACE^–/– and t-ACE^+/+ mice.

Results— In CA of t-ACE^–/– mice, blood pressure, outer diameter (D), and medial cross-sectional area (mCSA) were reduced, whereas blood flow (BF) and the number of medial cells (mC) were not modified. In the ligated CA, mCSA and number of mC were increased while outer D and distensibility were reduced. These changes were significantly less pronounced in t-ACE^–/– than t-ACE^+/+ mice. In UA of t-ACE^–/– mice, D was larger and mCSA was unaltered. At term pregnancy, D and mCSA of the UA were reversibly increased. Structural changes of UA during and after pregnancy were comparable in both strains.

Conclusions— t-ACE contributes to arterial structure and remodeling. It plays a major role in hyperplastic inward remodeling of the CA imposed by blood flow cessation, but it is not essential for outward hypertrophic and subsequent inward hypotrophic remodeling of the UA during and after pregnancy.

Key Words: tissue ACE • uterine artery • carotid artery • pregnancy • flow-induced remodeling • knockout mice

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