Temporal expression and activation of matrix metalloproteinases-2, -9, and @entity5781 following acute hindlimb XXXX .

@entity5781 @entity63 @entity19 @entity5780 @entity1235 @entity22534
OBJECTIVE: Matrix metalloproteinase (MMP) activity is essential for remodeling of @entity63 tissue. The @entity19 hindlimb @entity63 model exhibits tissue remodeling including revascularization in part due to angiogenesis. @entity22534 are type IV collagenases necessary for basement membrane degradation as a part of extracellular matrix remodeling and angiogenesis. Polymorphonuclear leukocytes (PMNs) contain @entity1235 , and in the presence of @entity5781 , are able to activate proMMP-2 in vitro. Activation of @entity22534 may be essential in @entity63 limbs both for tissue remodeling and revascularization via angiogenesis. We hypothesized that @entity22534 would be activated following acute hindlimb @entity63 (HI), and this activation would be temporally related to PMN infiltration. DESIGN OF STUDY: HI was achieved by unilateral femoral artery ligation in 20 FVB/ @entity19 . Five @entity19 underwent sham operation without hindlimb @entity63 . Gastrocnemius muscle was harvested from both hindlimbs at 1, 3, 14, and 30 days following ligation and assayed for @entity22534 (gelatin zymography), and @entity5781 (Western blotting). @entity22534 expression and activation were analyzed by gelatin zymography and quantified by densitometry with NIH Image Analysis software. Neutrophils per high power field were counted. The results were expressed as a ratio of @entity63 to nonischemic limbs and compared at each time point using ANOVA. RESULTS: Zymographic analysis revealed a 212% increase in active @entity5780 3 days postligation (P <.05). Active @entity1235 reached its maximum level (800% over baseline) on postoperative day 3 and continued to be elevated on day 14 (737% over baseline) (P <.05). The increase in active @entity22534 levels paralleled PMN infiltration that also peaked 3 days postligation (1184% over baseline) (P <.05). PMN count, @entity22534 all returned to baseline levels by postoperative Day 30. @entity5781 was present in tissue samples from all time points as confirmed by Western blot. CONCLUSIONS: @entity63 causes an early activation of @entity22534 in temporal relation to PMN infiltration. HI may prime PMNs, leading to their sequestration in @entity63 tissue. Primed PMNs, along with constitutively expressed @entity5781 , may activate @entity22534 and enable tissue remodeling essential for limb revascularization and angiogenesis.
