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Articles in PresS, published online ahead of print June 13, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00082.2002
Submitted on January 31, 2002
Accepted on June 10, 2002
1 Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada
2 Physiology, University of Birmingham, Birmingham, United Kingdom
3 Biological Sciences, Oakland University, Rochester, Michigan, USA
* To whom correspondence should be addressed. E-mail: thaas{at}yorku.ca.
Capillary growth in skeletal muscle occurs via the dissimilar processes of abluminal sprouting or longitudinal splitting, which can be initiated by muscle stretch and elevated shear stress, respectively. The distinct morphological hallmarks of these types of capillary growth suggest that discrete sets of angiogenic mediators play a role in each situation. Because proteolysis and proliferation are two key steps associated with capillary growth, we tested whether differences in the regulation of matrix metalloproteinases (MMPs) or VEGF may be associated with the two types of capillary growth. We found significant increases in MMP-2 total protein and % activation, and MT1-MMP mRNA levels, compared to control after muscle stretch, but not after shear stress stimulation. In contrast, VEGF protein and endothelial cell proliferation increased following either angiogenic stimulus. We observed that MMP-2 regulation occurs independent of VEGF signalling, because VEGF did not induce MMP-2 production or activation in isolated endothelial cells. Our data suggest that the involvement of MMPs in capillary growth is dependent on the nature of the angiogenic stimulus.
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