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Matrix Metalloproteinase Activity Causes VEGFR‐2 Cleavage and Microvascular Rarefaction in Rat Mesentery
Author(s) -
TRAN EDWARD D.,
YANG MING,
CHEN ANDREW,
DELANO FRANK A.,
MURFEE WALTER L.,
SCHMIDSCHÖNBEIN GEERT W.
Publication year - 2011
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2011.00082.x
Subject(s) - matrix metalloproteinase , microcirculation , angiogenesis , rarefaction (ecology) , mesentery , extracellular matrix , medicine , pathology , chemistry , endocrinology , microbiology and biotechnology , biology , ecology , species diversity
Please cite this paper as : Tran, Yang, Chen, DeLano, Murfee and Schmid‐Schönbein (2011). Matrix Metalloproteinase Activity Causes VEGFR‐2 Cleavage and Microvascular Rarefaction in Rat Mesentery. Microcirculation 18 (3), 228–237. Abstract A complication of the spontaneously hypertensive rat (SHR) is microvascular rarefaction, defined by the loss of microvessels. However, the molecular mechanisms involved in this process remain incompletely identified. Recent work in our laboratory suggests that matrix metalloproteinases (MMPs) may play a role by cleavage of the vascular endothelial growth factor receptor 2 (VEGFR‐2). In order to further delineate the role for MMPs in microvascular rarefaction, the objective of the current study was to examine the relationship in the same tissue between MMP activity, VEGFR‐2 cleavage and rarefaction. Using an in vivo microzymographic technique, we show significantly enhanced levels of MMP‐1, ‐1/‐9, ‐7, and ‐8 activities, but not MMP‐2 and ‐3 activities, along mesenteric microvessels of the SHR compared to its normotensive control, Wistar Kyoto rat. Based on immunohistochemical methods, the SHR exhibited a decreased labeling of the extracellular, but not the intracellular, domain of VEGFR‐2 along mesenteric microvessels. Chronic MMP inhibition served to attenuate VEGFR‐2 cleavage and microvascular network rarefaction in the SHR mesentery. These results spatially link MMP‐induced VEGFR‐2 cleavage and rarefaction in the mesentery of the SHR and thus support the hypothesis that MMPs serve as regulators of microvascular dysfunction in hypertension.