共 51 条
Evidence for Rho-Kinase Activation in Patients With Pulmonary Arterial Hypertension
被引:123
作者:

Do E, Zhulanqiqige
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Fukumoto, Yoshihiro
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Takaki, Aya
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Tawara, Shunsuke
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Ohashi, Junko
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Nakano, Makoto
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Tada, Tomohiro
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Saji, Kenya
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Sugimura, Kohichiro
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Fujita, Hiroshi
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Hoshikawa, Yasushi
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h-index: 0
机构:
Tohoku Univ, Grad Sch Med, Dept Thorac Surg, Sendai, Miyagi 9808574, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Nawata, Jun
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Kondo, Takashi
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机构:
Tohoku Univ, Grad Sch Med, Dept Thorac Surg, Sendai, Miyagi 9808574, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Shimokawa, Hiroaki
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机构:
Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
机构:
[1] Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
[2] Tohoku Univ, Grad Sch Med, Dept Thorac Surg, Sendai, Miyagi 9808574, Japan
关键词:
Endothelial function;
Pulmonary hypertension;
Rho-kinase;
Signal transduction;
Vascular smooth muscle;
SMOOTH-MUSCLE-CELLS;
NITRIC-OXIDE SYNTHASE;
LONG-TERM INHIBITION;
CARDIOVASCULAR MEDICINE;
THERAPEUTIC TARGET;
CORONARY-ARTERIES;
PROTEIN;
BOSENTAN;
EXPRESSION;
FASUDIL;
D O I:
10.1253/circj.CJ-09-0135
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Background: Direct evidence for Rho-kinase activation in patients with pulmonary hypertension (PH) is still lacking. Methods and Results: Rho-kinase activity in circulating neutrophils was examined by determining the ratio of phosphorylated/total forms of myosin-binding subunit, a substrate of Rho-kinase, in 40 consecutive PH patients and 40 healthy controls. Next, Rho-kinase expression and activity was examined in isolated human lung tissues (5 patients with idiopathic pulmonary arterial hypertension [IPAH], 5 controls) and vascular reactivity of isolated small human pulmonary arteries in vitro (4 IPAH, 4 controls). Rho-kinase activity in circulating neutrophils was significantly increased in the PH patients overall compared with controls (P<0.0001). Significant correlations were noted between Rho-kinase activity and the severity and duration of PAH (all P<0.05). Rho-kinase expression and activity in isolated lung tissues also were significantly increased in the IPAH patients compared with the controls (both P<0.0001). Endothelium-dependent relaxation was markedly impaired and serotonin-induced contraction (in the absence of the endothelium) markedly enhanced in the PAH patients compared with the controls, and the hypercontraction to serotonin was abolished by hydroxyfasudil, a specific Rho-kinase inhibitor. Conclusions: These results provide the first direct evidence for Rho-kinase activation in patients with PAH, suggesting the therapeutic importance of Rho-kinase in the disorder. (Circ J 2009; 73: 1731-1739)
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页码:1731 / 1739
页数:9
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan

Shimokawa, Hiroaki
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机构: Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
[10]
Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina
[J].
Fukumoto, Yoshihiro
;
Mohri, Masahiro
;
Inokuchi, Kosuke
;
Ito, Akira
;
Hirakawa, Yoji
;
Masumoto, Akihiro
;
Hirooka, Yoshitaka
;
Takeshita, Akira
;
Shimokawa, Hiroaki
.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,
2007, 49 (03)
:117-121

Fukumoto, Yoshihiro
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Mohri, Masahiro
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Inokuchi, Kosuke
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Ito, Akira
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Hirakawa, Yoji
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Masumoto, Akihiro
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Hirooka, Yoshitaka
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Takeshita, Akira
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

Shimokawa, Hiroaki
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Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Aoba Ku, Sendai, Miyagi 9808575, Japan