Cardiovascular Research Advance Access first published online on December 12, 2007
This version [Corrected Proof] published online on January 17, 2008
Cardiovascular Research, doi:10.1093/cvr/cvm102
Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead
Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands
* Corresponding author. Tel: +31 20 444 8110; fax: +31 20 444 8255. E-mail address: v.vanhinsbergh{at}vumc.nl
Sprouting angiogenesis is an invasive process that involves proteolytic activities required for the degradation of the endothelial basement membrane, cell migration with removal of obstructing matrix proteins, and generation of space in the matrix to allow endothelial cells to form a proper lumen. In the last decade it has become clear that besides these matrix-degrading properties, proteases exert additional, more subtle functions that play a key role in angiogenesis. These functions are discussed with specific emphasis on membrane type-1 matrix metalloproteinase (MT1-MMP), other MMPs, and the related ADAMs (a disintegrin and metalloproteinase domain). Proteases modulate the balance between pro- and anti-angiogenic factors by activation and modification of growth factors and chemokines, ectodomain shedding with accompanied receptor activation, shedding of cytokines from membrane-bound precursors, and generation of (matrix) protein fragments that inhibit or activate angiogenesis. Furthermore, they participate in the recruitment of leukocytes and progenitor cells, which contribute to the onset and progression of angiogenesis. Proteases facilitate the mobilization of progenitor cells in the bone marrow as well as the entry of these cells and leukocytes into the angiogenic area. The interaction between pericytes and the newly formed endothelial tubes is accompanied by silencing of MMP activities. Better understanding of the various activities of proteases may be helpful in developing more specific inhibitors that could result in tailor-made modification of proteolytic activities in disease.
KEYWORDS Matrix metalloproteinases; Angiogenesis; Endothelium; Invasion; Proteases
Time for primary review 20 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Roy, J. Yang, and M. A. Moses Matrix Metalloproteinases As Novel Biomarkers and Potential Therapeutic Targets in Human Cancer J. Clin. Oncol., November 1, 2009; 27(31): 5287 - 5297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. De Smet, I. Segura, K. De Bock, P. J. Hohensinner, and P. Carmeliet Mechanisms of Vessel Branching: Filopodia on Endothelial Tip Cells Lead the Way Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Suriano, D. Chaudhuri, R. S. Johnson, E. Lambers, B. T. Ashok, R. Kishore, and R. K. Tiwari 17{beta}-Estradiol Mobilizes Bone Marrow-Derived Endothelial Progenitor Cells to Tumors Cancer Res., August 1, 2008; 68(15): 6038 - 6042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Silvestre, B. I. Levy, and A. Tedgui Mechanisms of angiogenesis and remodelling of the microvasculature Cardiovasc Res, May 1, 2008; 78(2): 201 - 202. [Full Text] [PDF]
|
|