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 language | English |
|---|---|
| Pages (from-to) | 1632-1644 |
| Number of pages | 13 |
| Journal | Journal of Clinical Investigation |
| Volume | 118 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2008 May 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Medicine(all)
Cite this
}
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 journal › Article
TY - JOUR
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=43049136576&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43049136576&partnerID=8YFLogxK
U2 - 10.1172/JCI29226
DO - 10.1172/JCI29226
M3 - Article
C2 - 18414683
AN - SCOPUS:43049136576
VL - 118
SP - 1632
EP - 1644
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 5
ER -