Open AccessCCR 7‐ CCL 19/ CCL 21 Axis is Essential for Effective Arteriogenesis in a Murine Model of Hindlimb Ischemia
Author(s) -
Nossent A. Yaël,
Bastiaansen Antonius J. N. M.,
Peters Erna A. B.,
Vries Margreet R.,
Aref Zeen,
Welten Sabine M. J.,
Jager Saskia C. A.,
Pouw Kraan Tineke C. T. M.,
Quax Paul H. A.
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.005281
Subject(s) - ccl19 , arteriogenesis , hindlimb , medicine , c c chemokine receptor type 7 , ccl21 , ischemia , chemokine receptor , anatomy , immunology , chemokine , endocrinology , receptor
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” C57 BL /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 C57 BL /6 mice. In clear contrast, chemokine genes Ccl19 , Ccl21a , and Ccl21c and the chemokine receptor CCR 7 were upregulated in C57 BL /6 mice 1 day after hindlimb ischemia, but not in BALB /C mice. CCL 19 and CCL 21 regulate migration and homing of T lymphocytes via CCR 7. When subjecting CCR 7 −/− / LDLR −/− mice to hindlimb ischemia, we observed a 20% reduction in blood flow recovery compared with that in LDLR −/− mice. Equal numbers of α‐smooth muscle actin–positive collateral arteries were found in the adductor muscles of both mouse strains, but collateral diameters were smaller in the CCR 7 −/− / LDLR −/− . Fluorescence‐activated cell sorter analyses showed that numbers of CCR 7 + T lymphocytes (both CD 4 + and CD 8 + ) 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 CD 4 + T lymphocytes were decreased in the draining lymph nodes of LDLR −/− mice compared with CCR 7 −/− / LDLR −/− mice. Conclusions These data show that CCR 7‐ CCL 19/ CCL 21 axis facilitates retention CD 4 + T lymphocytes at the site of collateral artery remodeling, which is essential for effective arteriogenesis.