Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells.
Cardiovasc Res
; 78(2): 376-84, 2008 May 01.
Article
in En
| MEDLINE
| ID: mdl-18267956
ABSTRACT
AIMS:
Vascular endothelial growth factor (VEGF)-induced endothelial cell migration and angiogenesis are associated with the vascular complications of diabetes mellitus, and adiponectin is an abundant plasma adipokine that exhibits salutary effects on endothelial function. We investigated whether adiponectin suppresses VEGF-induced migration and related signal transduction responses in human coronary artery endothelial cells (HCAECs). METHODS ANDRESULTS:
Using a modified Boyden chamber technique and a monolayer 'wound-healing' assay, both the recombinant adiponectin globular domain and full-length adiponectin protein potently suppressed the migration of HCAEC induced by VEGF. Adiponectin did not increase endothelial cell apoptosis, as measured by terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labelling assay. Adiponectin also suppressed VEGF-induced reactive oxygen species generation, activation of Akt, the mitogen-activated protein kinase ERK and the RhoGTPase RhoA, and induction of the formation of actin stress fibres and focal cellular adhesions. VEGF-stimulated cell migration was inhibited by activation of adenylyl cyclase with forskolin, and adiponectin treatment increased cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) enzymatic activity. Pharmacological inhibition of either adenylyl cyclase or PKA significantly abrogated the effect of adiponectin globular domain to suppress VEGF-induced cell migration.CONCLUSION:
Adiponectin suppresses VEGF-stimulated HCAEC migration via cAMP/PKA-dependent signalling, an important effect with implications for a regulatory role of adiponectin in vascular processes associated with diabetes and atherosclerosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Movement
/
Neovascularization, Physiologic
/
Endothelial Cells
/
Vascular Endothelial Growth Factor A
Limits:
Humans
Language:
En
Journal:
Cardiovasc Res
Year:
2008
Document type:
Article
Affiliation country: