Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque

• Published in: Atherosclerosis Vol. 180; no. 1; pp. 37 - 44
• Main Authors: Yoon, Young Won, Kwon, Hyuck Moon, Hwang, Ki-Chul, Choi, Eui-Young, Hong, Bum-kee, Kim, Dongsoo, Kim, Hyun-Seung, Cho, Sang Ho, Song, Kyung Soon, Sangiorgi, Giuseppe
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-05-2005; Elsevier
• Subjects: Adolescent; Adult; Aged; Antigens, CD - metabolism; Atherosclerosis (general aspects, experimental research); Basigin; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Cardiovascular system; Carotid Artery Diseases - metabolism; Carotid Artery Diseases - pathology; Coronary heart disease; Destabilizing atheroma; EMMPRIN; Extracellular Matrix Proteins - metabolism; Gelatin; Heart; Humans; Immunohistochemistry; Interleukin-1 - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Medical sciences; Middle Aged; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Destabilizing atheroma; EMMPRIN; Matrix metalloproteinases; Heart; Immunohistochemistry; Cell culture; Conservation; Cardiovascular disease; Smooth muscle; Heart ventricle; Vascular disease; Infiltrate; Atherosclerotic plaque; Blood vessel; Atherosclerosis; Bone marrow; Immunoblotting assay; Aorta; Extracellular matrix; Atheroma; Endarteriectomy; Ventricular failure; Human; Heart failure; Monocyte; Enzyme; Cytokine; Cell differentiation; Experimental study; Coronary heart disease; Artery; Peptidases; Carotid; Hydrolases; Circulatory system; Macrophage
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2004.11.021

From experimental and clinical studies it is known that matrix conservation and degradation by matrix metalloproteinases (MMPs) plays a major role in plaque progression and destabilization with related onset of acute vascular events such as acute coronary syndromes or cerebrovascular accidents. Recently, extracellular MMPs inducer (EMMPRIN) has been reported to induce and activate the expression of MMPs in myocardium and plays an important role in the ventricular remodeling in human heart failure. Similarly to heart failure myocardium, EMMPRIN may be expressed in human atheroma and play a role in the extracellular matrix (ECM) remodeling and atherogenic cell differentiation. This study was designed to investigate the possible biological role of EMMPRIN in human atheroma. Immunohistochemical analysis for MMPs and EMMPRIN was performed on human carotid endarterectomy specimens and control aortas. EMMPRIN showed significant immunoreactivity in human atherosclerotic carotid lesions, and was colocalized with macrophage/monocyte infiltrates in atherosclerotic intima, plaque itself and vascular smooth muscle cells (VSMCs). Zymography and Western blot analysis revealed EMMPRIN expression in the carotid atheromas, but not in the control aortas. Human bone marrow monocytes, which were cultured with atherogenic proinflammatory cytokine stimulation revealed increased EMMPRIN and MMPs expressions. ECM remodeling is under the control of induction and inhibition of matrix degrading protease and the novel MMP inducer, EMMPRIN may play a role in influx and differentiation of monocytes and destabilizing atheroma.