PMID- 24137180
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 6
IP  - 2
DP  - 2013 Aug
TI  - The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of 
      endothelial cells against advanced glycation end products through the nuclear 
      factor kappaB pathway.
PG  - 310-316
AB  - Accumulating evidence has demonstrated that the Rho/Rho-associated protein kinase 
      (Rho/ROCK) and nuclear factor kappaB (NF-kappaB) signaling pathways are involved in the 
      pathogenesis of diabetic vascular injury. In this study, we investigated the 
      beneficial effects of fasudil, a ROCK inhibitor, on vascular endothelial injury 
      induced by advanced glycation end products (AGEs) in vitro. Human umbilical vein 
      endothelial cells (HUVECs) were stimulated with AGEs and AGEs plus fasudil in 
      various concentrations for different time periods. Monocyte-endothelial cell 
      adhesion, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant 
      protein-1 (MCP-1) expression, protein expression and activation of Rho/ROCK, 
      activation of NF-kappaB and reactive oxygen species (ROS) production were evaluated. 
      Fasudil suppressed AGE-induced monocyte-endothelial adhesion. Fasudil also 
      reduced the mRNA and protein expression of VCAM-1 and MCP-1 in a concentration- 
      and time-dependent manner. Moreover, increases in the protein levels of Rho/ROCK 
      and ROCK activity mediated by AGEs were inhibited by the addition of fasudil. 
      Additionally, fasudil attenuated AGE-induced NF-kappaB-dependent transcriptional 
      activity and inhibition of NF-kappaB (IkappaB) phosphorylation. ROS production induced by 
      AGEs was also reduced by fasudil in HUVECs. The results suggest that ROCK 
      inhibition may protect the vascular endothelium against AGE-induced 
      monocyte-endothelial adhesion in vitro through the reduction of ROS generation 
      and the downregulation of NF-kappaB signaling. Thus, ROCK inhibition may be a novel 
      therapeutic approach for the treatment of vascular complications in diabetes.
FAU - Lu, Yuyan
AU  - Lu Y
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai 200072;
FAU - Li, Hailing
AU  - Li H
FAU - Jian, Weixia
AU  - Jian W
FAU - Zhuang, Jianhui
AU  - Zhuang J
FAU - Wang, Ke
AU  - Wang K
FAU - Peng, Wenhui
AU  - Peng W
FAU - Xu, Yawei
AU  - Xu Y
LA  - eng
PT  - Journal Article
DEP - 20130520
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC3786857
OTO - NOTNLM
OT  - Rho kinase
OT  - advanced glycation end products
OT  - fasudil
OT  - nuclear factor kappaB
OT  - reactive oxygen species
EDAT- 2013/10/19 06:00
MHDA- 2013/10/19 06:01
PMCR- 2013/05/20
CRDT- 2013/10/19 06:00
PHST- 2013/02/08 00:00 [received]
PHST- 2013/05/07 00:00 [accepted]
PHST- 2013/10/19 06:00 [entrez]
PHST- 2013/10/19 06:00 [pubmed]
PHST- 2013/10/19 06:01 [medline]
PHST- 2013/05/20 00:00 [pmc-release]
AID - etm-06-02-0310 [pii]
AID - 10.3892/etm.2013.1125 [doi]
PST - ppublish
SO  - Exp Ther Med. 2013 Aug;6(2):310-316. doi: 10.3892/etm.2013.1125. Epub 2013 May 
      20.