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- Title
ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury.
- Authors
Noma, Kensuke; Rikitake, Yoshiyuki; Oyama, Naotsugu; Guijun Yan; Alcaide, Pilar; Ping-Yen Liu; Hongwei Wang; Ahl, Daniela; Sawada, Naoki; Okamoto, Ryuji; Hiroi, Yukio; Shimizu, Koichi; Luscinskas, Francis W.; Sun, Jianxin; Liao, James K.; Yan, Guijun; Liu, Ping-Yen; Wang, Hongwei
- Abstract
Although Rho-associated kinase (ROCK) activity has been implicated in cardiovascular diseases, the tissue- and isoform-specific roles of ROCKs in the vascular response to injury are not known. To address the role of ROCKs in this process, we generated haploinsufficient Rock1 (Rock1(+/-)) and Rock2 (Rock2(+/-)) mice and performed carotid artery ligations. Following this intervention, we found reduced neointima formation in Rock1(+/-) mice compared with that of WT or Rock2(+/-) mice. This correlated with decreased vascular smooth muscle cell proliferation and survival, decreased levels proinflammatory adhesion molecule expression, and reduced leukocyte infiltration. In addition, thioglycollate-induced peritoneal leukocyte recruitment and accumulation were substantially reduced in Rock1(+/-) mice compared with those of WT and Rock2(+/-) mice. To determine the role of leukocyte-derived ROCK1 in neointima formation, we performed reciprocal bone marrow transplantation (BMT) in WT and Rock1(+/-) mice. Rock1(+/-) to WT BMT led to reduced neointima formation and leukocyte infiltration following carotid ligation compared with those of WT to WT BMT. In contrast, WT to Rock1(+/-) BMT resulted in increased neointima formation. These findings indicate that ROCK1 in BM-derived cells mediates neointima formation following vascular injury and suggest that ROCK1 may represent a promising therapeutic target in vascular inflammatory diseases.
- Subjects
VASCULITIS; CARDIOVASCULAR diseases; LEUCOCYTES; ANIMAL models in research; VASCULAR smooth muscle; MEDICAL research; BLOOD-vessel physiology; CELL metabolism; PROTEIN metabolism; BONE marrow physiology; ANIMAL experimentation; ANTIGENS; BLOOD vessels; BONE marrow; BONE marrow transplantation; CAROTID artery; CELL physiology; CELLS; COMPARATIVE studies; RESEARCH methodology; MEDICAL cooperation; MICE; PHOSPHOTRANSFERASES; PROTEINS; RESEARCH; SMOOTH muscle; THROMBIN; EVALUATION research; ANATOMY
- Publication
Journal of Clinical Investigation, 2008, Vol 118, Issue 5, p1632
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI29226