Document Detail


Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator.
MedLine Citation:
PMID:  15307819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MMPs (matrix metalloproteinases) play a major role in the pathogenesis of hypertension by altering the extracellular matrix during cardiovascular remodelling. In the present study we show that MMP-2, but not MMP-9, cleaves the vasodilator peptide AM (adrenomedullin). Addition of the AM-binding protein, complement factor H, prevents this cleavage, providing a hitherto unknown mechanism of action for this binding protein. We identified the signature cleavage fragments and found some of them in human urine, suggesting that MMP-2 processing of AM may occur in vivo. Synthetic AM fragments regulated blood pressure in rats. The larger peptides are vasodilators, as is intact AM, whereas intermediate fragments did not affect blood pressure. In contrast, AM(11-22) elicited vasoconstriction. Studies of AM receptor activation in Rat2 cells confirm that the larger AM cleavage peptides activated this receptor, whereas AM(11-22) did not. The present study defines a new mechanism through which MMP-2 may regulate blood pressure by simultaneously eliminating a vasodilator and generating a vasoconstrictor.
Authors:
Alfredo Martínez; Hae-Ryong Oh; Edward J Unsworth; Claudia Bregonzio; Juan M Saavedra; William G Stetler-Stevenson; Frank Cuttitta
Related Documents :
2907589 - Amelioration of the hypotensive effect of trypanocidal diamidines by use of heavy solub...
6689129 - Anion influence on the binding of divalent cations to phosphatidylcholine.
3021389 - Vasoactive role of endogenous digoxin-like factor in rats with experimental hypertension.
6657559 - Effects of acute ochratoxicosis on blood pressure and heart rate of broiler chickens.
17143069 - Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.
18690609 - Canine drowning.
11473569 - Cardiovascular effects of beta 3-adrenoceptor stimulation in perinephritic hypertension.
24079679 - Characteristics of resistant hypertension in a large, ethnically diverse hypertension p...
16083509 - Complications after cryosurgery with new miniature cryoprobes in long hollow bones: an ...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Biochemical journal     Volume:  383     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-25     Completed Date:  2005-05-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  413-8     Citation Subset:  IM    
Affiliation:
Cell and Cancer Biology Branch and Vascular Biology Faculty, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. martinea@mail.nih.gov
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adrenomedullin
Animals
Blood Pressure
Cell Line
Chemical Fractionation / methods
Chromatography, High Pressure Liquid / methods
Cyclic AMP / metabolism
Fibroblasts / chemistry,  cytology
Humans
Hypertension / drug therapy
Hypotension / drug therapy
Male
Matrix Metalloproteinase 2 / metabolism*
Peptide Fragments / metabolism
Peptides / chemistry,  metabolism*,  urine
Rats
Rats, Inbred Lew
Receptors, Adrenomedullin
Receptors, Peptide / metabolism
Substrate Specificity
Urine / chemistry
Vasoconstrictor Agents / metabolism*
Vasodilator Agents / metabolism*
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Peptides; 0/Receptors, Adrenomedullin; 0/Receptors, Peptide; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 148498-78-6/Adrenomedullin; 60-92-4/Cyclic AMP; EC 3.4.24.24/Matrix Metalloproteinase 2
Comments/Corrections
Comment In:
Biochem J. 2004 Nov 1;383(Pt. 3):e5-7   [PMID:  15508185 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Localization of ferrochelatase in Plasmodium falciparum.
Next Document:  Regulation of GLUT1-mediated glucose uptake by PKClambda-PKCbeta(II) interactions in 3T3-L1 adipocyt...