Adiponectin Stimulates Angiogenesis by Promoting Cross-talk between AMP-activated Protein Kinase and Akt Signaling in Endothelial Cells*

By N. Ouchi, Hideki Kobayashi, S. Kihara, M. Kumada, Kaori Sato, Tatsuya Inoue, T. Funahashi, K. Walsh. Journal of Biological Chemistry, 2004

782 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/afb1f41264c7459d45e43b198190d44535c8568f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. H. Fang
2. R. L. Judd
3. K. Walsh
4. Barry J. Goldstein
5. Rosario Scalia
6. P. Scherer
7. N. Ouchi
8. T. Funahashi

In Molecular Biology

1. H. Fang
2. R. L. Judd
3. K. Walsh
4. P. Scherer
5. Barry J. Goldstein
6. Rosario Scalia
7. Sushil Kumar Jain
8. A. Achari

In Oncology

1. Barry J. Goldstein
2. Rosario Scalia

Citations in the corpus

• Adiponectin: A novel adipokine linking adipocytes and vascular function. (2004, positive): “AMP kinase also appears to mediate adiponectin signaling in endothelial cells (40, 41).”
• Adiponectin Regulation and Function (2018, positive): “Adiponectin stimulates the growth of new blood vessels by promoting cross-talk between AMPK and Akt signaling pathways, leading to the phosphorylation and activation of eNOS (236).”
• Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction (2017, background): “Mechanistically, many of the adiponectin benefits connected to its vasculoprotective are carried out via its ability to increases nitric oxide production through the activation of eNOS by AMPK-dependent manner [74,75].”
• Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis Through Adipose Tissue Crosstalk (2016, background): “Adiponectin stimulates angiogenesis through activation of AMPK and AKT in vivo and in vitro, thereby promoting endothelial nitric oxide synthesis within the endothelial cell (Ouchi et al., 2004).”
• Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2–dependent mechanisms (2005, background): “Adiponectin-activated AMPK signaling in endothelial cells is proangiogeni”