Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling.
Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties, and its plasma levels are reduced in association with obesity-linked diseases. Here, we investigated whether adiponectin regulates angiogenesis in response to tissue ischemia using adiponectin knock-out (KO) mice. Angiogenic repair of ischemic hind limbs was impaired in adiponectin-KO mice compared with wild-type (WT) mice as evaluated by laser Doppler flow method and capillary density analyses. Adenovirus-mediated supplement of adiponectin accelerated angiogenic repair in both adiponectin-KO and WT mice. Intramuscular injection of an adenovirus encoding dominant-negative AMP-activated kinase diminished the improvement in limb perfusion seen in WT mice and abolished the adiponectin-induced enhancement of perfusion. These data indicate that adiponectin can function to stimulate angiogenesis in response to ischemic stress by promoting AMP-activated kinase signaling. Therefore, adiponectin may be useful in the treatment for obesity-related vascular deficiency diseases.
Shibata
Rei
R
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street W611, Boston, Massachusetts 02118 , USA.
Ouchi
Noriyuki
N
Kihara
Shinji
S
Sato
Kaori
K
Funahashi
Tohru
T
Walsh
Kenneth
K
D055372:AMP-Activated Protein Kinases; D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D036341:Intercellular Signaling Peptides and Proteins; D007511:Ischemia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D009765:Obesity; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D052242:Adiponectin; D000911:Antibodies, Monoclonal; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases