ROCKs as therapeutic targets in cardiovascular diseases

被引:70
作者
Rikitake, Yoshiyuki [1 ,2 ]
Liao, James K. [1 ,2 ]
机构
[1] Brigham & Womens Hosp, Boston, MA 02115 USA
[2] Harvard Med Sch, Vasc Med Res Unit, Cardiovasc Div, Dept Med, Boston, MA 02115 USA
关键词
contraction; endothelium; hypertension; inflammation; leukocyte; remodeling; Rho-kinase; smooth muscle;
D O I
10.1586/14779072.3.3.441
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There is growing evidence that Rho-kinases (ROCKs), the immediate downstream targets of the small guanosine triphosphate-binding protein Rho, may contribute to cardiovascular disease. ROCKs play a central role in diverse cellular functions such as smooth muscle contraction, stress fiber formation and cell migration and proliferation. Overactivity of ROCKs is observed in cerebral ischemia, coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis and atherosclerosis. ROCKs, therefore, may be an important and still relatively unexplored therapeutic target in cardiovascular disease. Recent experimental and clinical studies using ROCK inhibitors such as Y-27632 and fasudil have revealed a critical role of ROCKs in embryonic development, inflammation and oncogenesis. This review will focus on the potential role of ROCKs in cellular functions and discuss the prospects of ROCK inhibitors as emerging therapy for cardiovascular diseases.
引用
收藏
页码:441 / 451
页数:11
相关论文
共 104 条
[1]   Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats [J].
Abe, K ;
Shimokawa, H ;
Morikawa, K ;
Uwatoku, T ;
Oi, K ;
Matsumoto, Y ;
Hattori, T ;
Nakashima, Y ;
Kaibuchi, K ;
Sueishi, K ;
Takeshita, A .
CIRCULATION RESEARCH, 2004, 94 (03) :385-393
[2]   Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase [J].
Amano, M ;
Chihara, K ;
Kimura, K ;
Fukata, Y ;
Nakamura, N ;
Matsuura, Y ;
Kaibuchi, K .
SCIENCE, 1997, 275 (5304) :1308-1311
[3]   The COOH terminus of Rho-kinase negatively regulates Rho-kinase activity [J].
Amano, M ;
Chihara, K ;
Nakamura, N ;
Kaneko, T ;
Matsuura, Y ;
Kaibuchi, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (45) :32418-32424
[4]   Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase) [J].
Amano, M ;
Ito, M ;
Kimura, K ;
Fukata, Y ;
Chihara, K ;
Nakano, T ;
Matsuura, Y ;
Kaibuchi, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (34) :20246-20249
[5]   Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury [J].
Bao, WK ;
Hu, E ;
Tao, L ;
Boyce, R ;
Mirabile, R ;
Thudium, DT ;
Ma, XL ;
Willette, RN ;
Yue, TL .
CARDIOVASCULAR RESEARCH, 2004, 61 (03) :548-558
[6]   RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction [J].
Bivalacqua, TJ ;
Champion, HC ;
Usta, MF ;
Cellek, S ;
Chitaley, K ;
Webb, RC ;
Lewis, RL ;
Mills, TM ;
Hellstrom, WJG ;
Kadowitz, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (24) :9121-9126
[7]  
Bourguignon LYW, 1999, CELL MOTIL CYTOSKEL, V43, P269, DOI 10.1002/(SICI)1097-0169(1999)43:4<269::AID-CM1>3.0.CO
[8]  
2-5
[9]   Characterization of RhoA-binding kinase ROKα implication of the pleckstrin homology domain in ROKα function using region-specific antibodies [J].
Chen, XQ ;
Tan, I ;
Ng, CH ;
Hall, C ;
Lim, L ;
Leung, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) :12680-12688
[10]   The Rho-associated protein kinase p160ROCK is required for centrosome positioning [J].
Chevrier, V ;
Piel, M ;
Collomb, N ;
Saoudi, Y ;
Frank, R ;
Paintrand, M ;
Narumiya, S ;
Bornens, M ;
Job, D .
JOURNAL OF CELL BIOLOGY, 2002, 157 (05) :807-817