Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque.
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.
Yoon
Young Won
YW
Department of Internal Medicine and Cardiovascular Division, YongDong Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Kwon
Hyuck Moon
HM
Hwang
Ki-Chul
KC
Choi
Eui-Young
EY
Hong
Bum-kee
BK
Kim
Dongsoo
D
Kim
Hyun-Seung
HS
Cho
Sang Ho
SH
Song
Kyung Soon
KS
Sangiorgi
Giuseppe
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D051926:Basigin; D015153:Blotting, Western; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005780:Gelatin; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D015703:Antigens, CD; C497886:BSG protein, human; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051926:Basigin; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9