title: ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury.
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.
authors.affiliation: Vascular Medicine Research Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Oyama
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.forename: Pilar
authors.initials: P
authors.lastname: Alcaide
authors.forename: Ping-Yen
authors.initials: PY
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Daniela
authors.initials: D
authors.lastname: Ahl
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawada
authors.forename: Ryuji
authors.initials: R
authors.lastname: Okamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiroi
authors.forename: Koichi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Francis W
authors.initials: FW
authors.lastname: Luscinskas
authors.forename: Jianxin
authors.initials: J
authors.lastname: Sun
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016026:Bone Marrow Transplantation; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000473:pathology; D049109:Cell Proliferation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C515854:Rock1 protein, mouse; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D013917:Thrombin