| First Author | Nossent AY | Year | 2017 |
| Journal | J Am Heart Assoc | Volume | 6 |
| Issue | 3 | PubMed ID | 28275068 |
| Mgi Jnum | J:274145 | Mgi Id | MGI:6296682 |
| Doi | 10.1161/JAHA.116.005281 | Citation | Nossent AY, et al. (2017) CCR7-CCL19/CCL21 Axis is Essential for Effective Arteriogenesis in a Murine Model of Hindlimb Ischemia. J Am Heart Assoc 6(3) |
| abstractText | BACKGROUND: In order to identify factors that stimulate arteriogenesis after ischemia, we followed gene expression profiles in two extreme models for collateral artery formation over 28 days after hindlimb ischemia, namely "good-responding" C57BL/6 mice and "poor-responding" BALB/c mice. METHODS AND RESULTS: Although BALB/c mice show very poor blood flow recovery after ischemia, most known proarteriogenic genes were upregulated more excessively and for a longer period than in C57BL/6 mice. In clear contrast, chemokine genes Ccl19, Ccl21a, and Ccl21c and the chemokine receptor CCR7 were upregulated in C57BL/6 mice 1 day after hindlimb ischemia, but not in BALB/C mice. CCL19 and CCL21 regulate migration and homing of T lymphocytes via CCR7. When subjecting CCR7(-/-)/LDLR(-/-) mice to hindlimb ischemia, we observed a 20% reduction in blood flow recovery compared with that in LDLR(-/-) mice. Equal numbers of alpha-smooth muscle actin-positive collateral arteries were found in the adductor muscles of both mouse strains, but collateral diameters were smaller in the CCR7(-/-)/LDLR(-/-). Fluorescence-activated cell sorter analyses showed that numbers of CCR7(+) T lymphocytes (both CD4(+) and CD8(+)) were decreased in the spleen and increased in the blood at day 1 after hindlimb ischemia in LDLR(-/-) mice. At day 1 after hindlimb ischemia, however, numbers of activated CD4(+) T lymphocytes were decreased in the draining lymph nodes of LDLR(-/-) mice compared with CCR7(-/-)/LDLR(-/-) mice. CONCLUSIONS: These data show that CCR7-CCL19/CCL21 axis facilitates retention CD4(+) T lymphocytes at the site of collateral artery remodeling, which is essential for effective arteriogenesis. |
