Matrix metalloproteinase-dependent EGF receptor activation in hypertension and left ventricular hypertrophy.
Agonist stimulation of certain G protein-coupled receptors (GPCRs) causes shedding of heparin-binding epidermal growth factor (HB-EGF) through activation of matrix metalloproteinases (MMPs), with subsequent transactivation of the EGF receptor. MMPs are widely expressed, and their dysregulated expression is crucial in cancer, inflammation, and cardiovascular remodeling. Recent studies in hypertensive animals have shown enhanced expression and activation of MMPs and EGF receptors, and their inhibition attenuates cardiac hypertrophy, vasoconstriction and hypertension induced by GPCR agonists such as angiotensin II, endothelin-1 and phenylepherine. These findings suggest that selective inhibition of MMPs might have therapeutic potential in hypertension and other cardiovascular diseases.
Shah
Bukhtiar H
BH
Section on Hormonal Regulation, ERRB/NICHD, National Institutes of Health, Bethesda, MD 20892-4510, USA. shahb@mail.nih.gov
Catt
Kevin J
KJ
D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors; D020782:Matrix Metalloproteinases