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


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.
Department of Surgery, University of Florida, Gainesville, Florida, USA. bercesa@surgery.ufl.edu
Scott A
SA
Berceli
Zhihua
Z
Jiang
Nina V
NV
Klingman
Gregory S
GS
Schultz
C Keith
CK
Ozaki
D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000637:transplantation*; D002339:Carotid Arteries; D017364:Collagenases / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression; D006439:Hemodynamics; D018056:Hemorheology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D017539:Tunica Intima / Q000033:anatomy & histology; D014680:Veins / Q000033:anatomy & histology / Q000637:transplantation*
D004792:Enzyme Precursors; D012333:RNA, Messenger; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9