Abstract
Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis (eNOS) in HUVECs. Transduction with either dominant-negative AMPK or dominant-negative Akt abolished adiponectin-induced eNOS phosphorylation as well as adiponectin-stimulated HUVEC migration and differentiation. Dominant-negative AMPK also inhibited adiponectin-induced Akt phosphorylation, suggesting that AMPK is upstream of Akt. Dominant-negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin-stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation. Finally, adiponectin stimulated blood vessel growth in vivo in mouse Matrigel plug implantation and rabbit corneal models of angiogenesis. These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
AMP-Activated Protein Kinases
-
Adenoviridae / genetics
-
Adiponectin
-
Animals
-
Blotting, Western
-
Cell Differentiation
-
Cell Movement
-
Cells, Cultured
-
Chromones / pharmacology
-
Collagen / chemistry
-
Collagen / pharmacology
-
Drug Combinations
-
Endothelial Cells / metabolism
-
Endothelium, Vascular / cytology
-
Enzyme Inhibitors / pharmacology
-
Genes, Dominant
-
Humans
-
Intercellular Signaling Peptides and Proteins*
-
Laminin / chemistry
-
Laminin / pharmacology
-
Mice
-
Models, Biological
-
Morpholines / pharmacology
-
Multienzyme Complexes / metabolism
-
Neovascularization, Pathologic
-
Nitric Oxide Synthase / metabolism
-
Nitric Oxide Synthase Type II
-
Nitric Oxide Synthase Type III
-
Phosphatidylinositol 3-Kinases / metabolism
-
Phosphorylation
-
Protein Serine-Threonine Kinases / metabolism
-
Proteins / chemistry*
-
Proteins / metabolism
-
Proteoglycans / chemistry
-
Proteoglycans / pharmacology
-
Rabbits
-
Recombinant Proteins / chemistry
-
Signal Transduction
-
Time Factors
-
Umbilical Veins / cytology
Substances
-
Adiponectin
-
Chromones
-
Drug Combinations
-
Enzyme Inhibitors
-
Intercellular Signaling Peptides and Proteins
-
Laminin
-
Morpholines
-
Multienzyme Complexes
-
Proteins
-
Proteoglycans
-
Recombinant Proteins
-
matrigel
-
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
Collagen
-
NOS3 protein, human
-
Nitric Oxide Synthase
-
Nitric Oxide Synthase Type II
-
Nitric Oxide Synthase Type III
-
Nos3 protein, mouse
-
Protein Serine-Threonine Kinases
-
AMP-Activated Protein Kinases