ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. 2008

Kensuke Noma, and Yoshiyuki Rikitake, and Naotsugu Oyama, and Guijun Yan, and Pilar Alcaide, and Ping-Yen Liu, and Hongwei Wang, and Daniela Ahl, and Naoki Sawada, and Ryuji Okamoto, and Yukio Hiroi, and Koichi Shimizu, and Francis W Luscinskas, and Jianxin Sun, and James K Liao
Vascular Medicine Research Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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.

UI MeSH Term Description Entries
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D016026 Bone Marrow Transplantation The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION. Bone Marrow Cell Transplantation,Grafting, Bone Marrow,Transplantation, Bone Marrow,Transplantation, Bone Marrow Cell,Bone Marrow Grafting
D017539 Tunica Intima The innermost layer of an artery or vein, made up of one layer of endothelial cells and supported by an internal elastic lamina. Internal Elastic Lamella,Internal Elastic Lamina,Tunica Intima Vasorum,Vascular Intima,Arterial Intima,Venous Intima,Arterial Intimas,Elastic Lamella, Internal,Elastic Lamina, Internal,Internal Elastic Laminas,Intima, Arterial,Intima, Vascular,Intima, Venous,Lamella, Internal Elastic,Lamina, Internal Elastic,Vascular Intimas,Venous Intimas
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

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