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A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats
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Matrix metalloproteinase-dependent EGF receptor activation in hypertension and left ventricular hypertrophy

Bukhtiar H Shah1, Kevin J Catt

  • 1Section on Hormonal Regulation, ERRB/NICHD, National Institutes of Health, Bethesda, MD 20892-4510, USA. shahb@mail.nih.gov

Trends in Endocrinology and Metabolism: TEM
|September 11, 2004
PubMed

Insights

Selective inhibition of matrix metalloproteinases (MMPs) may treat hypertension. MMPs are involved in G protein-coupled receptor (GPCR) activation, shedding of heparin-binding epidermal growth factor (HB-EGF), and EGF receptor transactivation, processes implicated in cardiovascular remodeling.

Area of Science:

  • Biochemistry
  • Cardiovascular Biology
  • Molecular Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) mediate cellular responses through signaling pathways.
  • Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix degradation and remodeling.
  • Heparin-binding epidermal growth factor (HB-EGF) shedding and EGF receptor transactivation are implicated in cardiovascular pathophysiology.

Purpose of the Study:

  • To investigate the role of MMPs in GPCR-mediated cardiovascular effects.
  • To explore the therapeutic potential of MMP inhibition in hypertension.

Main Methods:

  • Studies in hypertensive animal models.
  • Assessment of MMP and EGF receptor expression and activation.
  • Evaluation of the effects of MMP inhibitors on GPCR agonist-induced responses.

Main Results:

  • GPCR agonist stimulation leads to HB-EGF shedding via MMP activation and subsequent EGF receptor transactivation.
  • Enhanced MMP and EGF receptor expression and activation were observed in hypertensive animals.
  • Inhibition of MMPs attenuated cardiac hypertrophy, vasoconstriction, and hypertension induced by GPCR agonists.

Conclusions:

  • MMPs play a critical role in GPCR-mediated cardiovascular remodeling and hypertension.
  • Selective MMP inhibition shows therapeutic promise for hypertension and related cardiovascular diseases.

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