Published online before print April 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.1204715v1 78/1/195    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, M. P. Articles by Wahl, L. M. Search for Related Content PubMed PubMed Citation Articles by Kim, M. P. Articles by Wahl, L. M.

(Journal of Leukocyte Biology. 2005;78:195-201.)
© 2005 by Society for Leukocyte Biology

Angiotensin II increases human monocyte matrix metalloproteinase-1 through the AT₂ receptor and prostaglandin E₂: implications for atherosclerotic plaque rupture

Min P. Kim^*,, Min Zhou^* and Larry M. Wahl^*,1

^* 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:

				H. Jarvelainen, A. Sainio, M. Koulu, T. N. Wight, and R. Penttinen Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy Pharmacol. Rev., June 1, 2009; 61(2): 198 - 223. [Abstract] [Full Text] [PDF]

				E. Sanchez-Lemus, J. Benicky, J. Pavel, I. M. Larrayoz, J. Zhou, M. Baliova, T. Nishioku, and J. M. Saavedra Angiotensin II AT1 blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1376 - R1384. [Abstract] [Full Text] [PDF]

				M. H Barreta, J. F. C Oliveira, R. Ferreira, A. Q Antoniazzi, B. G Gasperin, L. R Sandri, and P. B. D Goncalves Evidence that the effect of angiotensin II on bovine oocyte nuclear maturation is mediated by prostaglandins E2 and F2{alpha} Reproduction, December 1, 2008; 136(6): 733 - 740. [Abstract] [Full Text] [PDF]

				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]