ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury

Kensuke Noma, Yoshiyuki Rikitake, Naotsugu Oyama, Guijun Yan, Pilar Alcaide, Ping Yen Liu, Hongwei Wang, Daniela Ahl, Naoki Sawada, Ryuji Okamoto, Yukio Hiroi, Koichi Shimizu, Francis W. Luscinskas, Jianxin Sun, James K. Liao

Research output: Contribution to journalArticle

129 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1632-1644
Number of pages13
JournalJournal of Clinical Investigation
Volume118
Issue number5
DOIs
StatePublished - May 1 2008

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Neointima
Vascular System Injuries
Leukocytes
Bone Marrow Transplantation
Ligation
Thioglycolates
rho-Associated Kinases
Vascular Diseases
Vascular Smooth Muscle
Carotid Arteries
Smooth Muscle Myocytes
Blood Vessels
Cell Survival
Protein Isoforms
Cardiovascular Diseases
Cell Proliferation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Noma, K., Rikitake, Y., Oyama, N., Yan, G., Alcaide, P., Liu, P. Y., ... Liao, J. K. (2008). ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. Journal of Clinical Investigation, 118(5), 1632-1644. https://doi.org/10.1172/JCI29226
Noma, Kensuke ; Rikitake, Yoshiyuki ; Oyama, Naotsugu ; Yan, Guijun ; Alcaide, Pilar ; Liu, Ping Yen ; Wang, Hongwei ; Ahl, Daniela ; Sawada, Naoki ; Okamoto, Ryuji ; Hiroi, Yukio ; Shimizu, Koichi ; Luscinskas, Francis W. ; Sun, Jianxin ; Liao, James K. / ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 5. pp. 1632-1644.
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Noma, K, Rikitake, Y, Oyama, N, Yan, G, Alcaide, P, Liu, PY, Wang, H, Ahl, D, Sawada, N, Okamoto, R, Hiroi, Y, Shimizu, K, Luscinskas, FW, Sun, J & Liao, JK 2008, 'ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury', Journal of Clinical Investigation, vol. 118, no. 5, pp. 1632-1644. https://doi.org/10.1172/JCI29226

ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. / Noma, Kensuke; Rikitake, Yoshiyuki; Oyama, Naotsugu; Yan, Guijun; Alcaide, Pilar; Liu, Ping Yen; Wang, Hongwei; Ahl, Daniela; Sawada, Naoki; Okamoto, Ryuji; Hiroi, Yukio; Shimizu, Koichi; Luscinskas, Francis W.; Sun, Jianxin; Liao, James K.

In: Journal of Clinical Investigation, Vol. 118, No. 5, 01.05.2008, p. 1632-1644.

Research output: Contribution to journalArticle

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T1 - ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury

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 - 2008/5/1

Y1 - 2008/5/1

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.

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