PMID- 22694757
OWN - NLM
STAT- MEDLINE
DCOM- 20121221
LR  - 20211021
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 11
DP  - 2012 Jun 13
TI  - ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 
      expression and monocyte-endothelial cell adhesion.
PG  - 65
LID - 10.1186/1475-2840-11-65 [doi]
AB  - BACKGROUND: Previous studies suggested that the RhoA/ROCK pathway may contribute 
      to vascular complications in diabetes. The present study was designed to 
      investigate whether ROCK inhibitor fasudil could prevent high glucose-induced 
      monocyte-endothelial cells adhesion, and whether this was related to fasudil 
      effects on vascular endothelial cell expression of chemotactic factors, vascular 
      cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). 
      METHODS: HUVECs were stimulated with high glucose (HG) or HG + fasudil in 
      different concentration or different time. Monocyte-endothelial cell adhesion was 
      determined using fluorescence-labeled monocytes. The mRNA and protein expression 
      of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The 
      protein levels of RhoA, ROCKI and p-MYPT were determined using western blot 
      analysis. ELISA was employed to measure the expression of soluble VCAM-1 and 
      MCP-1 in cell supernatants and human serum samples. RESULTS: Fasudil 
      significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced 
      Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG 
      induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also 
      decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 
      shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment 
      significantly decreased serum MCP-1 level from 27.9 +/- 10.6 pg/ml to 13.8 +/- 7.0 
      pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 +/- 7.5 ng/ml to 39.7 +/- 5.6 
      ng/ml after fasudil treatment (P < 0.05). CONCLUSIONS: Treatment with the 
      Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial 
      cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. 
      These results suggest inhibition of Rho/ROCK signaling may have therapeutic 
      potential in preventing diabetes associated vascular inflammation and 
      atherogenesis.
FAU - Li, Hailing
AU  - Li H
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Peng, Wenhui
AU  - Peng W
FAU - Jian, Weixia
AU  - Jian W
FAU - Li, Yuanmin
AU  - Li Y
FAU - Li, Qi
AU  - Li Q
FAU - Li, Weiming
AU  - Li W
FAU - Xu, Yawei
AU  - Xu Y
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120613
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - Q0CH43PGXS (fasudil)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/administration & dosage/*analogs & 
      derivatives/pharmacology
MH  - Aged
MH  - Anti-Inflammatory Agents/administration & dosage/pharmacology
MH  - Blotting, Western
MH  - Cell Adhesion/*drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/genetics/*metabolism
MH  - Chemotaxis, Leukocyte/drug effects
MH  - China
MH  - Coculture Techniques
MH  - Diabetes Mellitus/blood/drug therapy/enzymology/immunology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/*metabolism
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/enzymology/immunology
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Monocytes/*drug effects/immunology
MH  - Protein Kinase Inhibitors/administration & dosage/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Single-Blind Method
MH  - Time Factors
MH  - Vascular Cell Adhesion Molecule-1/blood/genetics/*metabolism
MH  - rho-Associated Kinases/*antagonists & inhibitors/metabolism
PMC - PMC3461463
EDAT- 2012/06/15 06:00
MHDA- 2012/12/22 06:00
PMCR- 2012/06/13
CRDT- 2012/06/15 06:00
PHST- 2012/04/25 00:00 [received]
PHST- 2012/06/06 00:00 [accepted]
PHST- 2012/06/15 06:00 [entrez]
PHST- 2012/06/15 06:00 [pubmed]
PHST- 2012/12/22 06:00 [medline]
PHST- 2012/06/13 00:00 [pmc-release]
AID - 1475-2840-11-65 [pii]
AID - 10.1186/1475-2840-11-65 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2012 Jun 13;11:65. doi: 10.1186/1475-2840-11-65.