ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury
| Autor: | Kensuke Noma, Ping Yen Liu, Yukio Hiroi, Pilar Alcaide, Francis W. Luscinskas, Guijun Yan, James K. Liao, Naotsugu Oyama, Ryuji Okamoto, Yoshiyuki Rikitake, Daniela Ahl, Jianxin Sun, Naoki Sawada, Koichi Shimizu, Hong-Wei Wang |
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| Rok vydání: | 2008 |
| Předmět: |
Neointima
medicine.medical_specialty Vascular smooth muscle Myocytes Smooth Muscle Intercellular Adhesion Molecule-1 Vascular Cell Adhesion Molecule-1 Bone Marrow Cells Biology Muscle Smooth Vascular Proinflammatory cytokine Mice Internal medicine Leukocytes medicine Animals Protein Isoforms Myocyte ROCK1 ROCK2 Bone Marrow Transplantation Cell Proliferation Mice Knockout rho-Associated Kinases Thrombin General Medicine medicine.disease Mice Inbred C57BL Carotid Arteries Endocrinology Immunology Tunica Intima Infiltration (medical) Research Article |
| Zdroj: | Journal of Clinical Investigation. 118:1632-1644 |
| ISSN: | 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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