Cathepsin L is required for endothelial progenitor cell-induced neovascularization
Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sites of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 837933
- Report Number(s):
- LBNL-55523; R&D Project: LGFGAA; TRN: US200507%%65
- Journal Information:
- Nature Medicine, Vol. 11, Issue 2; Other Information: Submitted to Nature Medicine: Volume 11, No.2; Journal Publication Date: 02/2005; PBD: 15 Jan 2004
- Country of Publication:
- United States
- Language:
- English
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