| First Author | Hoefer IE | Year | 2002 |
| Journal | Circulation | Volume | 105 |
| Issue | 14 | Pages | 1639-41 |
| PubMed ID | 11940540 | Mgi Jnum | J:103226 |
| Mgi Id | MGI:3608752 | Doi | 10.1161/01.cir.0000014987.32865.8e |
| Citation | Hoefer IE, et al. (2002) Direct evidence for tumor necrosis factor-alpha signaling in arteriogenesis. Circulation 105(14):1639-41 |
| abstractText | BACKGROUND: Arteriogenesis serves as an efficient mechanism for flow restoration after arterial occlusion. This process is associated with inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), although their role in arteriogenesis remains unclear. We hypothesized that arteriogenesis is reduced in mice lacking functional TNF-alpha or p55 receptor. To test this hypothesis, we developed a novel microsphere-based murine model of hindlimb perfusion measurement. METHODS AND RESULTS: Unilateral femoral arteries of nude (n=9), TNF-alpha(-/-) (n=9), TNF-alpha receptor p55(-/-) (n=8), and p75(-/-) (n=8) mice as well as their appropriate genetic background controls were occluded. The nude mice underwent laser Doppler hindlimb flux measurements preoperatively, postoperatively, and after 7 days. Seven days after ligation, all animals underwent tissue perfusion determinations using fluorescent microspheres. Laser Doppler findings confirmed acute decrease in flux with falsely normal values after 1 week. Microsphere results from control mice showed perfusion restoration to values approximately 50% of normal within 7 days. TNF-alpha(-/-) mice demonstrated a significant reduction (45.1%) in collateral artery perfusion compared with controls (TNF-alpha(-/-) 22.4+/-5.1% versus B6x129 49.7+/-9.3%; P<0.01). p55(-/-) mice exhibited an almost identical 45.8% reduction in collateral artery formation (p55(-/-) 28.3+/-4.3% versus C57BL/6J 61.8+/-9.1%; P<0.01), whereas p75(-/-) mice were equivalent to controls (p75(-/-) 54.5+/-5.5%; P=0.13). CONCLUSIONS: Microsphere techniques in mice offer a tool for the molecular dissection of arteriogenesis mechanisms. These results suggest that TNF-alpha positively modulates arteriogenesis probably via signaling through its p55 receptor. |
