scholarly journals Rho-Kinase Inhibition Ameliorates Dasatinib-Induced Endothelial Dysfunction and Pulmonary Hypertension

2018 ◽  
Vol 9 ◽  
Author(s):  
Csilla Fazakas ◽  
Chandran Nagaraj ◽  
Diana Zabini ◽  
Attila G. Végh ◽  
Leigh M. Marsh ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Rho Kinase ◽  
Kinase Inhibition

scholarly journals Effects of Rho-Kinase Inhibition on Pulmonary Hypertension, Lung Growth, and Structure in Neonatal Rats Chronically Exposed to Hypoxia

2010 ◽  
Vol 67 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Adrian J A Ziino ◽  
Julijana Ivanovska ◽  
Rosetta Belcastro ◽  
Crystal Kantores ◽  
Emily Z Xu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rho Kinase ◽  
Neonatal Rats ◽  
Lung Growth ◽  
Kinase Inhibition

Animal models of pulmonary hypertension: Rho kinase inhibition

2012 ◽  
Vol 109 (3) ◽  
pp. 67-75 ◽  
Author(s):  
Amy L. Firth ◽  
Il-Whan Choi ◽  
Won Sun Park
Keyword(s):  
Pulmonary Hypertension ◽  
Animal Models ◽  
Rho Kinase ◽  
Kinase Inhibition

Long term Rho-kinase inhibition ameliorates endothelial dysfunction in LDL-Receptor deficient mice

2005 ◽  
Vol 512 (2-3) ◽  
pp. 247-249 ◽  
Author(s):  
Kerstin Steioff ◽  
Hartmut Rütten ◽  
Andreas E. Busch ◽  
Oliver Plettenburg ◽  
Yuri Ivashchenko ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Ldl Receptor ◽  
Rho Kinase ◽  
Kinase Inhibition ◽  
Deficient Mice

scholarly journals Rho-kinase inhibition alleviates pulmonary hypertension in transgenic mice expressing a dominant-negative type II bone morphogenetic protein receptor gene

2011 ◽  
Vol 301 (5) ◽  
pp. L667-L674 ◽  
Author(s):  
Tadashi Yasuda ◽  
Yuji Tada ◽  
Nobuhiro Tanabe ◽  
Koichiro Tatsumi ◽  
James West
Keyword(s):  
Pulmonary Hypertension ◽  
Kinase Activity ◽  
Pulmonary Arteries ◽  
Rho Kinase ◽  
Dominant Negative ◽  
Type Ii ◽  
Kinase Inhibition ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a sustained elevation in the pulmonary artery pressure and subsequent right heart failure. The activation of Rho/Rho-kinase activity and the beneficial effect of Rho-kinase inhibition have been demonstrated in several experimental models of pulmonary hypertension. However, it remains unclear whether Rho-kinase inhibitors can also be used against pulmonary hypertension associated with mutations in the type II bone morphogenetic protein receptor (BMPRII) gene. Transgenic mice expressing a dominant-negative BMPRII gene (with an arginine to termination mutation at amino acid 899) in smooth muscle by a tetracycline-gene switch system (SM22-tet-BMPR2R899X mice) were examined. They developed an elevated right ventricular systolic pressure (RVSP), right ventricular (RV) hypertrophy, muscularization of small pulmonary arteries, and an associated disturbed blood flow in their lungs. The Rho/Rho-kinase activity and Smad activity were determined by a Western blot analysis by detecting GTP-RhoA and the phosphorylation of myosin phosphatase target subunit 1, Smad1, and Smad2. In the lungs of SM22-tet-BMPR2R899X mice, the Rho/Rho-kinase activity was elevated significantly, whereas the Smad activity was almost unchanged. Fasudil, a Rho-kinase inhibitor, significantly decreased RVSP, alleviated RV hypertrophy and muscularization of small pulmonary arteries, and improved blood flow in SM22-tet-BMPR2R899X mice, although it did not alter Smad signaling. Our study demonstrates that Rho/Rho-kinase signaling is activated via a Smad-independent pathway in an animal model of pulmonary hypertension with a BMPRII mutation in the cytoplasmic tail domain. Rho-kinase inhibition is therefore a possible therapeutic approach for the treatment of PAH associated with genetic mutation.

scholarly journals The Neuroprotective Potential of Rho-Kinase Inhibition in Promoting Cell Survival and Reducing Reactive Gliosis in Response to Hypoxia in Isolated Bovine Retina

2013 ◽  
Vol 32 (1) ◽  
pp. 218-234 ◽  
Author(s):  
Aizhan Alt ◽  
Ralf-Dieter Hilgers ◽  
Aysegül Tura ◽  
Khaled Nassar ◽  
Toni Schneider ◽  
...  
Keyword(s):  
Cell Survival ◽  
Rho Kinase ◽  
Reactive Gliosis ◽  
Kinase Inhibition ◽  
Bovine Retina

scholarly journals Rho-Kinase Inhibition During Early Cardiac Development Causes Arrhythmogenic Right Ventricular Cardiomyopathy in Mice

2015 ◽  
Vol 35 (10) ◽  
pp. 2172-2184 ◽  
Author(s):  
Alia Ellawindy ◽  
Kimio Satoh ◽  
Shinichiro Sunamura ◽  
Nobuhiro Kikuchi ◽  
Kota Suzuki ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Cardiac Development ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Rho Kinase ◽  
Ventricular Cardiomyopathy ◽  
Kinase Inhibition ◽  
Early Cardiac Development

The effect of Rho Kinase inhibition on corneal nerve regeneration in vitro and in vivo

2021 ◽  
Author(s):  
Sonja Mertsch ◽  
Inga Neumann ◽  
Cosima Rose ◽  
Marc Schargus ◽  
Gerd Geerling ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Rho Kinase ◽  
Kinase Inhibition ◽  
Corneal Nerve ◽  
Regeneration In Vitro

scholarly journals The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling

2014 ◽  
Vol 307 (4) ◽  
pp. H628-H632 ◽  
Author(s):  
Sheila Flavahan ◽  
Nicholas A. Flavahan
Keyword(s):  
Laser Scanning ◽  
Rho Kinase ◽  
Laser Scanning Microscopy ◽  
Scanning Microscopy ◽  
Stress Fibers ◽  
Light Chains ◽  
Myosin Light Chains ◽  
Kinase Signaling ◽  
No Donor ◽  
Kinase Inhibition

Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [ postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase ( NG-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling.

Induction of the Stem-like Cell Regulator CD44 by Rho Kinase Inhibition Contributes to the Maintenance of Colon Cancer–Initiating Cells

2012 ◽  
Vol 72 (19) ◽  
pp. 5101-5110 ◽  
Author(s):  
Hirokazu Ohata ◽  
Tatsuya Ishiguro ◽  
Yuki Aihara ◽  
Ai Sato ◽  
Hiroaki Sakai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Rho Kinase ◽  
Kinase Inhibition
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