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Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular Diseases

Xiaoyu Liu1, John Fassett, Yidong Wei

  • 1Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

Evidence-Based Complementary and Alternative Medicine : Ecam
|July 24, 2013
PubMed

Insights

Asymmetric dimethylarginine (ADMA) increases cardiovascular risk by inhibiting nitric oxide. Targeting the enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH1) via farnesoid X receptor (FXR) agonists may restore nitric oxide bioavailability and treat heart failure.

Area of Science:

  • Cardiovascular Science
  • Molecular Biology
  • Pharmacology

Background:

  • Asymmetric dimethylarginine (ADMA) inhibits nitric oxide synthase, reducing nitric oxide (NO) bioavailability.
  • Elevated ADMA levels are linked to increased mortality in general populations and post-myocardial infarction patients.
  • Congestive heart failure is characterized by higher ADMA content in plasma and tissues.

Purpose of the Study:

  • To explore the role of dimethylarginine dimethylaminohydrolase-1 (DDAH1) in ADMA metabolism.
  • To investigate the potential of farnesoid X receptor (FXR) agonists in modulating DDAH1 expression.
  • To assess the therapeutic potential of targeting DDAH1 for cardiovascular diseases.

Main Methods:

  • Review of recent studies on ADMA, DDAH1, and FXR.
  • Analysis of the impact of FXR activation on DDAH1 expression.
  • Evaluation of FXR agonists like ursodeoxycholic acid (UDCA) and GW4064.

Main Results:

  • DDAH1 is identified as the key enzyme responsible for ADMA degradation.
  • Activation of FXR by UDCA or GW4064 leads to increased DDAH1 expression.
  • This suggests a mechanism for controlling ADMA levels and NO bioavailability.

Conclusions:

  • Modulating DDAH1 activity via FXR agonists represents a promising therapeutic strategy.
  • Targeting the FXR-DDAH1 pathway could improve NO bioavailability in conditions like congestive heart failure.
  • This approach offers a potential treatment for cardiovascular diseases associated with reduced NO production.

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