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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:208.)
© 2001 American Heart Association, Inc.

Vascular Biology

Low Blood Flow After Angioplasty Augments Mechanisms of Restenosis

Inward Vessel Remodeling, Cell Migration, and Activity of Genes Regulating Migration

Michael R. Ward; Philip S. Tsao; Alex Agrotis; Rodney J. Dilley; Garry L. Jennings; Alex Bobik

From the Cell Biology Laboratory, Baker Medical Research Institute, and Alfred Baker Medical Unit (M.R.W., A.A., R.J.D., G.L.J., A.B.), Alfred Hospital, Prahran, Victoria, Australia, and the Department of Cardiovascular Medicine (M.R.W., P.S.T.), Stanford University, Stanford, Calif.

Correspondence to Dr Michael Ward, MBBS, PhD, Department of Cardiology, Royal North Shore Hospital, St Leonards NSW 2065, Australia. E-mail mrward{at}doh.health.nsw.gov.au

Abstract—The predominant cause of restenosis after angioplasty is now thought to be inward remodeling, but the mechanisms responsible are unknown. Remodeling in normal vessels is regulated by the endothelium in response to altered shear stress. Although the endothelium is often damaged by angioplasty, restenosis rates after angioplasty have been correlated with impaired coronary flow. Thus, we examined how increases or decreases in blood flow through balloon catheter–injured rat carotid arteries affect vessel morphometry (4, 10, and 28 days), cell migration (4 days), and levels of promigratory mRNAs (2 and 10 days). After 28 days, the luminal area in vessels with low blood flow was significantly less than in those with normal and high blood flow (0.17±0.01 [low] versus 0.24±0.06 [normal] versus 0.30±0.02 [high] mm², P<0.01), predominantly because of accentuated inward remodeling (or reduced area within the external elastic lamina; 0.42±0.02 [low] versus 0.54±0.07 [normal] versus 0.53±0.04 [high] mm², P<0.05). Low flow also enhanced smooth muscle cell migration 4 days after injury by 90% above normal and high flows (P<0.01). Two days after injury, low flow significantly increased levels of mRNAs encoding promigratory peptides (integrin _vß₃, transforming growth factor-ß₁, CD44v6, MDC9, urokinase plasminogen activator receptor, and ß-inducible gene h3); these changes persisted 10 days after injury and were localized to the neointima. Low blood flow may promote restenosis after angioplasty because of its adverse effect on vessel remodeling, and it is associated with the augmented expression of multiple genes central to cell migration and restenosis.

Key Words: angioplasty • restenosis • remodeling • blood flow

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