| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print April 7, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, and
Howard Hughes Medical Institute–National Institutes of Health Research Scholar, Bethesda, Maryland
1 Correspondence: Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Building 30, Room 325, Bethesda, MD 20892-4352. E-mail: lwahl{at}dir.nidcr.nih.gov
Angiotensin II (Ang II)-mediated hypertension increases the risk for acute coronary syndrome, a consequence of atherosclerotic plaque rupture, which may be caused by matrix metalloproteinases (MMPs). Here, we show that human primary monocytes stimulated with tumor necrosis factor 
(TNF-) and granulocyte macrophage-colony stimulating factor (GM-CSF) release Ang II, which is an integral component of the signal transduction pathway that leads to MMP-1 production. An Ang II-mediated increase in MMP-1 synthesis occurred only in conjunction with cytokine stimulation. Moreover, Ang II mediated its effect through the Ang II type 2 (AT2) receptor, as demonstrated by enhancement of MMP-1 production by an AT2 agonist, CGP-42112A, and inhibition of MMP-1 production by PD1233319, an AT2 antagonist. Additionally, exogenous Ang II caused a significant enhancement in MMP-1 production by cytokine-stimulated monocytes, and the most effective enhancement occurrred when Ang II was added 6 h after stimulation. Furthermore, Ang II and the AT2 agonist increased prostaglandin E2 (PGE2), which in turn mediated the increase in MMP-1, as shown by the inhibition of MMP-1 by indomethacin or aspirin. In contrast, the AT2 antagonist inhibited the PGE2 production induced by TNF- and GM-CSF. Ang II, through its interaction with the AT2 receptor, has a central role in mediating the PGE2-dependent production of MMP-1 by monocytes stimulated with TNF- and GM-CSF. These observations provide insight into the association between hypertension and acute coronary syndrome and a possible mechanism by which Ang-converting enzyme inhibitor and aspirin may reduce the risk for heart attacks.
Key Words: angiotensin II receptor subtype 2 • inflammation • cytokines
This article has been cited by other articles:
|
|
 |
|
  R. Ferreira, J. F. Oliveira, R. Fernandes, J. F. Moraes, and P. B. Goncalves The role of angiotensin II in the early stages of bovine ovulation Reproduction, November 1, 2007; 134(5): 713 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yusof, K. Kamada, F. Spencer Gaskin, and R. J. Korthuis Angiotensin II mediates postischemic leukocyte-endothelial interactions: role of calcitonin gene-related peptide Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3032 - H3037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cuenca, P. Martin-Sanz, A. M. Alvarez-Barrientos, L. Bosca, and N. Goren Infiltration of Inflammatory Cells Plays an Important Role in Matrix Metalloproteinase Expression and Activation in the Heart during Sepsis Am. J. Pathol., November 1, 2006; 169(5): 1567 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Strauss and A. S. Hall Angiotensin Receptor Blockers May Increase Risk of Myocardial Infarction: Unraveling the ARB-MI Paradox Circulation, August 22, 2006; 114(8): 838 - 854. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bolbrinker, S. Markovic, M. Wehland, W. B. W. H. Melenhorst, H. van Goor, and R. Kreutz Expression and Response to Angiotensin-Converting Enzyme Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Glomerular Damage in Young Transgenic Rats with Renin-Dependent Hypertension J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
