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Atorvastatin modulates the DDAH1/ADMA system in high-fat diet-induced insulin-resistant rats with endothelial

Po Chen1, Ke Xia, Zhenyu Zhao

  • 1Cardiology Department, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

Vascular Medicine (London, England)
|November 28, 2012
PubMed

Insights

Atorvastatin improved endothelial function in insulin-resistant rats by modulating dimethylarginine dimethyl-aminohydrolase 1 (DDAH1) and asymmetric dimethylarginine (ADMA) levels. This suggests a potential therapeutic role for atorvastatin in managing cardiovascular risks associated with insulin resistance.

Area of Science:

  • Cardiovascular Pharmacology
  • Metabolic Research
  • Endothelial Biology

Background:

  • Insulin resistance is a key factor in endothelial dysfunction and cardiovascular diseases.
  • Dimethylarginine dimethyl-aminohydrolase 1 (DDAH1) metabolizes asymmetric dimethylarginine (ADMA), impacting endothelial function.
  • Atorvastatin is recognized for its endothelium-protective properties.

Purpose of the Study:

  • To investigate the effects of atorvastatin on the DDAH1/ADMA pathway in a rat model of insulin resistance.
  • To explore the correlation between insulin sensitivity and DDAH activity.

Main Methods:

  • Insulin resistance was induced in male Sprague-Dawley rats using an 8-week high-fat diet.
  • Atorvastatin (30 mg/kg/day) was administered for an additional 8 weeks to a subset of rats.
  • DDAH activity, aortic DDAH1 and sterol regulatory element-binding protein 1 (SREBP1) expression, and plasma ADMA levels were measured.

Main Results:

  • Insulin-resistant rats showed decreased DDAH activity and aortic DDAH1/SREBP1 expression, alongside elevated plasma ADMA.
  • Atorvastatin treatment reversed these changes, inhibiting the increase in ADMA and restoring DDAH activity and DDAH1 expression.
  • A significant positive correlation was observed between insulin sensitivity and DDAH activity.

Conclusions:

  • Atorvastatin may improve endothelial function in insulin resistance by modulating the DDAH1/ADMA pathway.
  • The findings suggest a potential therapeutic mechanism for atorvastatin in cardiovascular disease prevention related to metabolic dysfunction.
  • Sterol regulatory element-binding protein 1 (SREBP1) may also be involved in the observed effects.

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