This Article Full Text Full Text (PDF) All Versions of this Article: 22/7/1200    most recent 01.ATV.0000021411.53577.1Cv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Major, T. C. Articles by Bocan, T. M.A. Search for Related Content PubMed PubMed Citation Articles by Major, T. C. Articles by Bocan, T. M.A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Related Collections Coumarins Acute coronary syndromes Coagulation and fibronolysis Endothelium/vascular type/nitric oxide

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1200.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Is Induced Upon Monocyte Differentiation and Is Expressed in Human Atheroma

Terry C. Major; Liang Liang; Xiaokang Lu; Wendy Rosebury; Thomas M.A. Bocan

From the Cardiovascular Pharmacology, Pfizer Global Research & Development, Pfizer, Inc, Ann Arbor, Mich.

Correspondence to Terry C. Major, Cardiovascular Pharmacology, Pfizer Global Research & Development, Pfizer, Inc, 2800 Plymouth Rd, Ann Arbor, MI 48105. E-mail terry.major{at}pfizer.com

Objective— Because extracellular matrix metalloproteinase inducer (EMMPRIN), a tumor cell–derived protein, induces matrix metalloproteinases (MMPs) in fibroblasts and because MMPs are important in atheroma formation, we investigated if EMMPRIN was expressed in granulocyte/macrophage-colony stimulating factor (GM-CSF)–differentiated human peripheral blood monocytes (HPBM) and macrophage foam cells. In addition, EMMPRIN was studied for its expression in human atheroma.

Methods and Results— After 10 days of GM-CSF–induced monocyte differentiation, EMMPRIN mRNA increased 5- to 8-fold relative to undifferentiated monocytes. GM-CSF treatment of HPBM revealed that both EMMPRIN mRNA and protein were upregulated by day 2 over undifferentiated monocytes. GM-CSF–differentiated HPBM showed characteristic macrophage phenotype by showing increases in pancake-like morphology and increases in biochemical markers such as apolipoprotein E, MMP-9, and cholesterol ester (CE). While acetylated LDL treatment of the 10-day GM-CSF–differentiated HPBM increased CE mass 13- to 321-fold, EMMPRIN expression was unchanged relative to nonlipid-loaded macrophages. In human coronary atherosclerotic samples, EMMPRIN was observed in CD68(+) macrophage-rich areas as well as areas of MMP-9 expressions.

Conclusions— Based on these data, we conclude that monocyte differentiation induces EMMPRIN expression, CE enrichment of foam cells has no further effect on EMMPRIN expression, and EMMPRIN is present in human atheroma. Therefore, EMMPRIN may play a role in atherosclerosis development.

Key Words: atherosclerosis • EMMPRIN (extracellular matrix metalloproteinase inducer) • cholesterol ester • human peripheral blood monocyte (HPBM) • matrix metalloproteinase-9 (MMP-9) • matrix metalloproteinase-1 (MMP-1)

This article has been cited by other articles:

				A. C. Newby Metalloproteinase Expression in Monocytes and Macrophages and its Relationship to Atherosclerotic Plaque Instability Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2108 - 2114. [Abstract] [Full Text] [PDF]

				D. T. Browman, M. E. Resek, L. D. Zajchowski, and S. M. Robbins Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER J. Cell Sci., August 1, 2006; 119(15): 3149 - 3160. [Abstract] [Full Text] [PDF]

				J. P.G. Sluijter, D. P.V. de Kleijn, and G. Pasterkamp Vascular remodeling and protease inhibition-bench to bedside Cardiovasc Res, February 15, 2006; 69(3): 595 - 603. [Abstract] [Full Text] [PDF]

				R. Schmidt, A. Bultmann, M. Ungerer, N. Joghetaei, O. Bulbul, S. Thieme, T. Chavakis, B. P. Toole, M. Gawaz, A. Schomig, et al. Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells: Implications in Acute Myocardial Infarction Circulation, February 14, 2006; 113(6): 834 - 841. [Abstract] [Full Text] [PDF]

				J. P.G. Sluijter, W. P.C. Pulskens, A. H. Schoneveld, E. Velema, C. F. Strijder, F. Moll, J.-P. de Vries, J. Verheijen, R. Hanemaaijer, D. P.V. de Kleijn, et al. Matrix Metalloproteinase 2 Is Associated With Stable and Matrix Metalloproteinases 8 and 9 With Vulnerable Carotid Atherosclerotic Lesions: A Study in Human Endarterectomy Specimen Pointing to a Role for Different Extracellular Matrix Metalloproteinase Inducer Glycosylation Forms Stroke, January 1, 2006; 37(1): 235 - 239. [Abstract] [Full Text] [PDF]

				T. Passioura, A. Dolnikov, S. Shen, and G. Symonds N-Ras-Induced Growth Suppression of Myeloid Cells Is Mediated by IRF-1 Cancer Res., February 1, 2005; 65(3): 797 - 804. [Abstract] [Full Text] [PDF]

				C. Haug, C. Lenz, F. Diaz, and M. G. Bachem Oxidized Low-Density Lipoproteins Stimulate Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Release by Coronary Smooth Muscle Cells Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1823 - 1829. [Abstract] [Full Text] [PDF]

				Y. Noguchi, T. Sato, M. Hirata, T. Hara, K. Ohama, and A. Ito Identification and Characterization of Extracellular Matrix Metalloproteinase Inducer in Human Endometrium during the Menstrual Cycle in Vivo and in Vitro J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6063 - 6072. [Abstract] [Full Text] [PDF]

				T. Betsuyaku, M. Tanino, K. Nagai, Y. Nasuhara, M. Nishimura, and R. M. Senior Extracellular Matrix Metalloproteinase Inducer Is Increased in Smokers' Bronchoalveolar Lavage Fluid Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 222 - 227. [Abstract] [Full Text] [PDF]