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Lindsey, M.L. et al.

Lindsey, Escobar, Dobrucki, Goshorn, Bouges, Mingoia, McClister, Su, Gannon, MacGillivray, Lee, Sinusas, Spinale,

Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction.

Matrix metalloproteinases (MMPs) are postulated to be necessary for neovascularization during wound healing. MMP-9 deletion alters remodeling postmyocardial infarction (post-MI), but whether and to what degree MMP-9 affects neovascularization post-MI is unknown. Neovascularization was evaluated in wild-type (WT; n = 63) and MMP-9 null (n = 55) mice at 7-days post-MI. Despite similar infarct sizes, MMP-9 deletion improved left ventricular function as evaluated by hemodynamic analysis. Blood vessel quantity and quality were evaluated by three independent studies. First, vessel density was increased in the infarct of MMP-9 null mice compared with WT, as quantified by Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) immunohistochemistry. Second, preexisting vessels, stained in vivo with FITC-labeled GSL-I pre-MI, were present in the viable but not MI region. Third, a technetium-99m-labeled peptide (NC100692), which selectively binds to activated alpha(v)beta3-integrin in angiogenic vessels, was injected into post-MI mice. Relative NC100692 activity in myocardial segments with diminished perfusion (0-40% nonischemic) was higher in MMP-9 null than in WT mice (383 +/- 162% vs. 250 +/- 118%, respectively; P = 0.002). The unique finding of this study was that MMP-9 deletion stimulated, rather than impaired, neovascularization in remodeling myocardium. Thus targeted strategies to inhibit MMP-9 early post-MI will likely not impair the angiogenic response.[1]

References

Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Lindsey, M.L., Escobar, G.P., Dobrucki, L.W., Goshorn, D.K., Bouges, S., Mingoia, J.T., McClister, D.M., Su, H., Gannon, J., MacGillivray, C., Lee, R.T., Sinusas, A.J., Spinale, F.G. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]

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