| First Author | Hodara R | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 10 | Pages | 2203-9 |
| PubMed ID | 21799178 | Mgi Jnum | J:191845 |
| Mgi Id | MGI:5463189 | Doi | 10.1161/ATVBAHA.111.233247 |
| Citation | Hodara R, et al. (2011) Overexpression of catalase in myeloid cells causes impaired postischemic neovascularization. Arterioscler Thromb Vasc Biol 31(10):2203-9 |
| abstractText | OBJECTIVE: Myeloid lineage cells (MLCs) such as macrophages are known to play a key role in postischemic neovascularization. However, the role of MLC-derived reactive oxygen species in this process and their specific chemical identity remain unknown. METHODS AND RESULTS: Transgenic mice with MLC-specific overexpression of catalase (Tg(Cat-MLC) mice) were created on a C57BL/6 background. Macrophage catalase activity was increased 3.4-fold compared with wild-type mice. After femoral artery ligation, laser Doppler perfusion imaging revealed impaired perfusion recovery in Tg(Cat-MLC) mice. This was associated with fewer collateral vessels, as assessed by microcomputed tomography angiography, and decreased capillary density. Impaired functional recovery of the ischemic limb was also evidenced by a 50% reduction in spontaneous running activity. The deficient neovascularization was associated with a blunted inflammatory response, characterized by decreased macrophage infiltration of ischemic tissues, and lower mRNA levels of inflammatory markers, such as tumor necrosis factor-alpha, osteopontin, and matrix mettaloproteinase-9. In vitro macrophage migration was impaired in Tg(Cat-MLC) mice, suggesting a role for H(2)O(2) in regulating the ability of macrophages to infiltrate ischemic tissues. CONCLUSIONS: MLC-derived H(2)O(2) plays a key role in promoting neovascularization in response to ischemia and is a necessary factor for the development of ischemia-induced inflammation. |
