This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Laszik, Z. G. Articles by Esmon, C. T. Search for Related Content PubMed PubMed Citation Articles by Laszik, Z. G. Articles by Esmon, C. T.

(American Journal of Pathology. 2001;159:797-802.)
© 2001 American Society for Investigative Pathology

Short Communications

Down-Regulation of Endothelial Expression of Endothelial Cell Protein C Receptor and Thrombomodulin in Coronary Atherosclerosis

Zoltan G. Laszik^*, Xin J. Zhou, Gary L. Ferrell, Fred G. Silva and Charles T. Esmon^*¶||

From the Departments of Pathology^* andBiochemistry and Molecular Biology,^¶ University ofOklahoma Health Sciences Center, the Howard Hughes MedicalInstitute and the CardiovascularBiology Research Program,^|| Oklahoma Medical ResearchFoundation, Oklahoma City, Oklahoma; the Department ofPathology, University of Texas SouthwesternMedical Center, Dallas, Texas; and the United States and CanadianAcademy of Pathology, Atlanta, Georgia

Coronary atherosclerosis with occlusive thrombosis is the major cause of acute myocardial infarction. Although plaque rupture is usually hypothesized to be the predisposing event in coronary thrombosis, the possibility cannot be excluded that local changes in the anticoagulant properties of the endothelium overlying the plaque contribute to this process. It is evident that thrombomodulin and the endothelial cell protein C receptor are critical players in the control of the thrombogenic process. This study examined whether thrombomodulin and the endothelial cell protein C receptor are down-regulated on endothelial cells overlying the atherosclerotic plaque in coronary arteries and thus could potentially favor local thrombus formation. Sections of archival left and right coronary arteries (n = 18 each) with severe atherosclerosis from the native heart of six patients who underwent heart transplantation were immunostained for CD31, CD34, endothelial cell protein C receptor, and thrombomodulin using a streptavidin-biotin-peroxidase method. Controls included left and right coronary arteries from autopsy cases with no atherosclerosis (n = 6), and also from cases with mild atherosclerosis (n = 5). The apparent density of all of these proteins was much higher in control than in atherosclerotic arteries. Our findings support the hypothesis that both endothelial cell protein C receptor and thrombomodulin are down-regulated in coronary arteries with atherosclerosis. These changes would be expected to result in reduced inhibition of thrombogenic and anti-inflammatory activity on the endothelium overlying atherosclerotic regions and thus could contribute to coronary thrombosis.

This article has been cited by other articles:

				L. Wang, J. A. Bastarache, N. Wickersham, X. Fang, M. A. Matthay, and L. B. Ware Novel Role of the Human Alveolar Epithelium in Regulating Intra-Alveolar Coagulation Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 497 - 503. [Abstract] [Full Text] [PDF]

				W. C. Aird Phenotypic Heterogeneity of the Endothelium: I. Structure, Function, and Mechanisms Circ. Res., February 2, 2007; 100(2): 158 - 173. [Abstract] [Full Text] [PDF]

				N. K. Kapur, C. B. Deming, S. Kapur, C. Bian, H. C. Champion, J. K. Donahue, D. A. Kass, and J. J. Rade Hemodynamic Modulation of Endocardial Thromboresistance Circulation, January 2, 2007; 115(1): 67 - 75. [Abstract] [Full Text] [PDF]

				K. Rabausch, E. Bretschneider, M. Sarbia, J. Meyer-Kirchrath, P. Censarek, R. Pape, J. W. Fischer, K. Schror, and A.-A. Weber Regulation of Thrombomodulin Expression in Human Vascular Smooth Muscle Cells by COX-2-Derived Prostaglandins Circ. Res., January 7, 2005; 96(1): e1 - e6. [Abstract] [Full Text] [PDF]

				D. Seo, T. Wang, H. Dressman, E. E. Herderick, E. S. Iversen, C. Dong, K. Vata, C. A. Milano, F. Rigat, J. Pittman, et al. Gene Expression Phenotypes of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1922 - 1927. [Abstract] [Full Text] [PDF]

				D. W. Sommeijer, A. Beganovic, C. G. Schalkwijk, H. Ploegmakers, C. M. van der Loos, B. E. van Aken, H. ten Cate, and A. C. van der Wal More Fibrosis and Thrombotic Complications but Similar Expression Patterns of Markers for Coagulation and Inflammation in Symptomatic Plaques from DM2 Patients J. Histochem. Cytochem., September 1, 2004; 52(9): 1141 - 1149. [Abstract] [Full Text] [PDF]

				M. Levi, T. van der Poll, and H. R. Buller Bidirectional Relation Between Inflammation and Coagulation Circulation, June 8, 2004; 109(22): 2698 - 2704. [Full Text] [PDF]

				C. T. Esmon The Protein C Pathway Chest, September 1, 2003; 124(3_suppl): 26S - 32S. [Abstract] [Full Text] [PDF]

				H. Ishii, T. Tezuka, H. Ishikawa, K. Takada, K. Oida, and S. Horie Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RAR{beta}-RXR{alpha} heterodimers and Sp1 and Sp3 to their binding sequences in the TM promoter Blood, June 15, 2003; 101(12): 4765 - 4774. [Abstract] [Full Text] [PDF]

				T. Goto, T. Baba, K. Matsuyama, K. Honma, M. Ura, and T. Koshiji Aortic atherosclerosis and postoperative neurological dysfunction in elderly coronary surgical patients Ann. Thorac. Surg., June 1, 2003; 75(6): 1912 - 1918. [Abstract] [Full Text] [PDF]

				K. Masamura, K. Oida, H. Kanehara, J. Suzuki, S. Horie, H. Ishii, and I. Miyamori Pitavastatin-Induced Thrombomodulin Expression by Endothelial Cells Acts Via Inhibition of Small G Proteins of the Rho Family Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 512 - 517. [Abstract] [Full Text] [PDF]

				P. K. Shah Mechanisms of plaque vulnerability and rupture J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 15S - 22S. [Abstract] [Full Text] [PDF]

				S. R. Lentz Thrombosis of Vein Grafts: Wall Tension Restrains Thrombomodulin Expression Circ. Res., January 10, 2003; 92(1): 12 - 13. [Full Text] [PDF]

				C. Kluft, R. Kleemann, and M.P.M. de Maat How best to counteract the enemies? By controlling inflammation in the coronary circulation Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G53 - G65. [Abstract] [PDF]

				C. T. Esmon New Mechanisms for Vascular Control of Inflammation Mediated by Natural Anticoagulant Proteins J. Exp. Med., September 2, 2002; 196(5): 561 - 564. [Full Text] [PDF]

				E. M. Conway, M. Van de Wouwer, S. Pollefeyt, K. Jurk, H. Van Aken, A. De Vriese, J. I. Weitz, H. Weiler, P. W. Hellings, P. Schaeffer, et al. The Lectin-like Domain of Thrombomodulin Confers Protection from Neutrophil-mediated Tissue Damage by Suppressing Adhesion Molecule Expression via Nuclear Factor {kappa}B and Mitogen-activated Protein Kinase Pathways J. Exp. Med., September 2, 2002; 196(5): 565 - 577. [Abstract] [Full Text] [PDF]

				T. S. Edgington So What Is Critically Lacking with Coronary Atherosclerotic Plaques? Perhaps the Antithrombotic Control Am. J. Pathol., September 1, 2001; 159(3): 795 - 796. [Full Text] [PDF]