Faculty Collaboration Database

Suppression of angiotensin-converting enzyme expression and activity by shear stress. Circ Res 1997 Mar;80(3):312-9

Date

03/01/1997

Pubmed ID

9048650

DOI

10.1161/01.res.80.3.312

Scopus ID

2-s2.0-0031043720 (requires institutional sign-in at Scopus site)   124 Citations

Abstract

Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE activity measured in bovine pulmonary artery endothelial (BPAE) cells was reduced by 49.5% after exposure to a shear stress of 20 dyne/cm2 for 18 hours. Short-term shearing (2 hours) elevated ACE activity in BPAE cells, whereas long-term shearing produced a time-dependent reduction in ACE activity by 23.3%, 33.5%, and 48.9% at 8, 12, and 18 hours, respectively. Northern blot analysis revealed that shear stress (20 dyne/cm2 for 18 hours) significantly reduced ACE mRNA expression by 82%. To determine the mechanism of ACE activity and message reduction, the effect of shear on transcriptionally related events was determined in a rabbit aortic endothelial cell line (W3LUC) stably transfected with 1.3 kb of a rat ACE promoter/luciferase construct. Different shear stress magnitudes (5 to 20 dyne/cm2) caused suppression of luciferase activity by an average of 40.7%. ACE promoter activity was suppressed by 2 hours of shear stress (24.7%) and was further inhibited at time periods > 8 hours. In vivo elevations in shear stress were created by placing a stainless steel clip over a 12-mm region of the rat abdominal aorta. Restriction of vessel diameter increased blood flow velocity and caused reduction in vascular ACE activity by 40%. These studies suggest that elevations in the level of shear stress alter endothelial cell function by suppressing ACE gene and protein expression in vitro and in vivo.

Author List

Rieder MJ, Carmona R, Krieger JE, Pritchard KA Jr, Greene AS

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Aorta
Biomechanical Phenomena
Cattle
Cells, Cultured
Constriction, Pathologic
Dose-Response Relationship, Drug
Endothelium, Vascular
Gene Expression Regulation
Male
Nitric Oxide Synthase
Norepinephrine
Peptidyl-Dipeptidase A
Promoter Regions, Genetic
Pulmonary Artery
Rabbits
Rats
Rats, Sprague-Dawley
Stress, Mechanical
Time Factors
Transfection