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J Surg Res. 2006 Aug;134(2):327-34. Epub 2006 Feb 20.

Early differential MMP-2 and -9 dynamics during flow-induced arterial and vein graft adaptations.

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  • 1Department of Surgery, University of Florida, Gainesville, Florida, USA. bercesa@surgery.ufl.edu

Abstract

BACKGROUND:

Arteries and vein grafts respond differently to reductions in flow, with arteries demonstrating inward remodeling through only limited structural reorganization of the media and vein grafts developing a thickened intima, with little change in the external diameter. In an effort to mechanistically explore the biology of this contrasting behavior, we hypothesized that this differential response in flow-mediated remodeling is driven by unique temporal expression patterns and functional activities of the matrix metalloproteinase (MMP)-2 and -9, key effectors of blood vessel architecture remodeling.

MATERIAL AND METHODS:

In rabbits, bilateral carotid vein grafting was coupled with unilateral partial distal ligation to create a sevenfold flow differential between sides. Vein grafts and proximal carotid arteries were then harvested for morphological and biochemical studies at time points ranging from 1 to 14 days.

RESULTS:

Vein grafts demonstrated an early, transient increase in pro-MMP-9 within adherent monocytes and endothelial cells. This was followed by a delayed increase in smooth muscle cell active MMP-2, which was coincident with the onset of intimal thickening at days 7 and 14 and significantly elevated by low flow. In contrast, arteries showed no elevation in pro MMP-9 above baseline, but demonstrated a transient increase in latent MMP-2 preceding the flow-mediated change in vessel diameter.

CONCLUSIONS:

These data provide evidence for unique and independent roles of MMP-2 and -9 in the process of hemodynamically driven vascular remodeling.

PMID:
16488440
[PubMed - indexed for MEDLINE]
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