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Differential effects of Rho-kinase inhibition on artery wall mass and remodeling.

Authors
  • Pearce, Jeffrey D
  • Li, Jing
  • Edwards, Matthew S
  • English, William P
  • Geary, Randolph L
Type
Published Article
Journal
Journal of Vascular Surgery
Publisher
Elsevier
Publication Date
Jan 01, 2004
Volume
39
Issue
1
Pages
223–228
Identifiers
PMID: 14718843
Source
Medline
License
Unknown

Abstract

Fasudil blocked SMC contraction of collagen gels in a dose-dependent manner. Complete inhibition of collagen gel remodeling was achieved between 10 and 30 micromol/L fasudil. In control mice, carotid ligation caused significant thickening of the adventitia, media, and intima (P <.01) and outward remodeling of the carotid wall. The external elastic lamina (EEL) area increased by 14% versus sham (P <.05), but this increase was insufficient to prevent lumen narrowing (-42% vs sham, P <.05). Fasudil treatment had favorable effects on wall mass, inhibiting neointimal (P =.04), medial (P =.03), and adventitial thickening (P =.07) versus controls. Opposite our hypothesis, however, fasudil did not enhance outward artery wall remodeling or improve lumen caliber. Rather, inhibiting Rho-kinase blocked outward remodeling in response to ligation. EEL area was significantly smaller in treated versus control animals (P =.04) and slightly smaller versus shams (P = NS). These data suggest that Rho activation contributes significantly to both hyperplasia and outward remodeling of the injured artery wall. Rho-kinase may prove an important target to limit intimal hyperplasia and prevent restenosis when remodeling is improved by other means (eg, stents).

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