ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury.

@article{citeulike:2744944, 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.}, address = {Vascular Medicine Research Unit, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, USA. Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.}, author = {Noma, Kensuke and Rikitake, Yoshiyuki and Oyama, Naotsugu and Yan, Guijun and Alcaide, Pilar and Liu, Ping-Yen Y. and Wang, Hongwei and Ahl, Daniela and Sawada, Naoki and Okamoto, Ryuji and Hiroi, Yukio and Shimizu, Koichi and Luscinskas, Francis W W. and Sun, Jianxin and Liao, James K K. }, citeulike-article-id = {2744944}, doi = {http://dx.doi.org/10.1172/JCI29226}, issn = {0021-9738}, journal = {The Journal of clinical investigation}, month = {April}, posted-at = {2008-05-02 11:34:36}, priority = {2}, title = {ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury.}, url = {http://dx.doi.org/10.1172/JCI29226}, year = {2008} }

TY - JOUR ID - citeulike:2744944 L3 - citeulike-article-id:2744944 TI - ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. JF - The Journal of clinical investigation AD - Vascular Medicine Research Unit, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, USA. Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA. SN - 0021-9738 N2 - 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. AU - Noma, Kensuke AU - Rikitake, Yoshiyuki AU - Oyama, Naotsugu AU - Yan, Guijun AU - Alcaide, Pilar AU - Liu, Ping-Yen AU - Wang, Hongwei AU - Ahl, Daniela AU - Sawada, Naoki AU - Okamoto, Ryuji AU - Hiroi, Yukio AU - Shimizu, Koichi AU - Luscinskas, Francis W AU - Sun, Jianxin AU - Liao, James K PY - 2008/04/15/ UR - http://dx.doi.org/10.1172/JCI29226 ER -