Nature Medicine11, 206 - 213 (2005)
Published online: 23 January 2005; | doi:10.1038/nm1182
Cathepsin L is required for endothelial progenitor cell−induced neovascularization
Carmen Urbich1, Christopher Heeschen1, Alexandra Aicher1, Ken-ichiro Sasaki1, Thomas Bruhl1, Mohammad R Farhadi2, Peter Vajkoczy2, Wolf K Hofmann3, Christoph Peters4, Len A Pennacchio5, Nasreddin D Abolmaali6, Emmanouil Chavakis1, Thomas Reinheckel4, Andreas M Zeiher1
& Stefanie Dimmeler1
1
Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590
Frankfurt, Germany.
2
Department of Neurosurgery, Medical Faculty of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167
Mannheim, Germany.
3
Department of Hematology and Oncology, Internal Medicine I, University of Frankfurt, Theodor-Stern-Kai 7, 60590
Frankfurt, Germany.
4
Department of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan-Meier-Strasse 17, 79104
Freiburg, Germany.
5
Department of Genome Sciences, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California
94720, USA.
6
Institute for Diagnostic and Interventional Radiology, University of Frankfurt, Theodor-Stern-Kai 7, 60590
Frankfurt, Germany.
Infusion of endothelial progenitor cells (EPC), but not of mature endothelial cells, promotes neovascularization after ischemia. We performed gene expression profiling of EPC and endothelial cells to identify genes that might be important for the neovascularization capacity of EPC. Notably, the protease cathepsin L (CathL) was highly expressed in EPC as opposed to endothelial cells and was essential for matrix degradation and invasion by EPC in vitro. CathL-deficient mice showed impaired functional recovery following hind limb ischemia, supporting the concept of a crucial role for CathL in postnatal neovascularization. Infused CathL-deficient progenitor cells neither homed to sites of ischemia nor augmented neovascularization. Forced expression of CathL in mature endothelial cells considerably enhanced their invasive activity and sufficed to confer their capacity for neovascularization in vivo. We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
