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(Circulation Research. 2007;100:749.)
© 2007 American Heart Association, Inc.

Editorials

The Matrix Revolutions

Matrix Metalloproteinase, Vasculogenesis, and Ischemic Tissue Repair

Marie-Ange Renault, Douglas W. Losordo

From the Feinberg Cardiovascular Research Institute and Program in Cardiovascular Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital (M.-A.R., D.W.L.), Chicago, Ill.

Correspondence to Douglas W. Losordo, MD; Feinberg Cardiovascular Research Institute and Northwestern Memorial Hospital, Tarry 12-703, 303 E. Chicago Avenue, Chicago, IL 60611. E-mail d-losordo@northwestern.edu

See related article, pages 904–913

Key Words: angiogenesis • vasculogenesis • matrix metalloproteinases

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The matrix metalloproteinase (MMP) family of Zinc dependent extracellular proteinases regulates development and physiologic events, including branching morphogenesis, angiogenesis, wound healing and extracellular matrix degradation. They are synthesized as secreted or transmembrane proenzymes and processed to an active form by the removal of an amino-terminal propeptide. MMP-2/Gelatinase A, as well as MMP-9/gelatinase B, which belong to the gelatinase subclass of the MMP family, have been shown to play a central role in initiating angiogenesis^1,2 and to be upregulated after hindlimb ischemia.³ They are involved in degrading extracellular and basement membrane structures, allowing endothelial migration to occur. In addition, MMPs promote the release of extracellular matrix-bound cytokines, such as vascular endothelial growth factor (VEGF), which can regulate angiogenesis.⁴

Both MMP-2 and MMP-9 expression have been shown to be upregulated in bone marrow and peripheral blood derived CD34 positive cells treated by stromal cell derived factor-1.⁵ Only MMP-9 had been shown to be involved in vasculogenesis and more particularly endothelial progenitor cell (EPC) mobilization. First, MMP-9 has been shown to be upregulated in the bone marrow and necessary for VEGF-, placental growth factor- and by stromal cell derived factor-1–induced EPC recruitment.^6,7,8 Increased MMP-9 activity in the bone marrow has been shown to induce the release of soluble kit ligand (skitL) promoting the proliferation and motility of hematopoietic stem cell and EPCs within the bone marrow.⁶ The role of MMP-9 in EPC mobilization has been confirmed in several studies. For example, it has been shown to be involved in estradiol (E₂)-induced neovascularization . . . [Full Text of this Article]