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Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic

Bee K Tan1, Raghu Adya, Jing Chen

  • 1Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.

Cardiovascular Research
|May 6, 2009
PubMed
Abstract

Insights

Thrombospondin-1 (TSP-1) levels are lower in women with polycystic ovary syndrome (PCOS). Metformin treatment increases circulating TSP-1, offering insights into obesity, insulin resistance, and angiogenesis in PCOS.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome
  • Vascular Biology

Background:

  • Polycystic ovary syndrome (PCOS) is linked to insulin resistance (IR), obesity, and cardiovascular issues.
  • Thrombospondin-1 (TSP-1), an antiangiogenic adipokine, is elevated in obese, insulin-resistant individuals.
  • The role of TSP-1 in PCOS pathophysiology, particularly in adipose tissue (AT), requires further investigation.

Purpose of the Study:

  • To quantify TSP-1 levels in adipose tissue of women with PCOS compared to controls.
  • To evaluate the impact of metformin on circulating TSP-1 in PCOS patients.
  • To assess the effects of serum from PCOS women on in vitro angiogenesis and the regulation of AT TSP-1 by glucose.

Main Methods:

  • Serum TSP-1, PAI-1, and PAI-1 activity measured by ELISA.
  • AT TSP-1 mRNA and protein analyzed using RT-PCR and Western blotting.
  • In vitro angiogenesis assays and ex vivo glucose regulation studies performed.

Main Results:

  • PCOS women exhibited lower AT and serum TSP-1 levels, with higher PAI-1 and PAI-1 activity.
  • Metformin treatment significantly increased serum TSP-1 and decreased PAI-1/PAI-1 activity in PCOS subjects.
  • Serum from PCOS women enhanced in vitro migration and angiogenesis, effects attenuated by metformin via NF-kappaB, Erk1/2, and Erk5 pathways.

Conclusions:

  • TSP-1 levels are reduced in women with PCOS.
  • Metformin therapy effectively increases serum TSP-1 levels in PCOS patients.
  • These findings elucidate novel connections between obesity, IR, and angiogenesis in PCOS.

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