Cardiovascular & Lipid Disorders

Gregory Retzinger

Gregory Retzinger, M.D., Ph.D.

Pathology & Lab Med

Professor

Director Clin Hemostasis

Research Summary

Of all the plasma proteins, fibrinogen, an adhesive protein and the precursor of the blood clot matrix, adsorbs preferentially to surfaces in contact with blood. Once bound, fibrinogen is predisposed to clot formation. A frequently observed consequence of this predisposition is the "clotting off" of circulatory prosthetics such as vascular grafts and heart valves. Thus, an aim of biomedical materials research is the synthesis of materials that do not bind fibrinogen in vivo. But fibrinogen does not adsorb to synthetic materials alone. Indeed, a host of naturally-occurring lipid surfaces — both physiologic and pathophysiologic -- bind fibrinogen. Such surfaces include the cytoplasmic membrane of activated platelets and macrophages, the cytoplasmic membrane of tumor cells, the luminal face of atherosclerotic plaques, and even the cell wall of virulent tubercle bacilli. Once bound to these surfaces, fibrinogen is also predisposed to clot. By focusing clot formation on these surfaces, fibrinogen makes the surfaces adhesive. This fibrin-mediated adhesion operates during a number of important processes as seemingly unrelated as platelet plug formation, phagocytosis, metastasis and atherogenesis. Thus, by studying the interactions of fibrin(ogen) with surfaces, lipid surfaces in particular, some mechanistic insight might be gleaned relevant to the treatment of human disease.

Gregory Retzinger, Ph.D., M.D., has developed model systems with which to probe the role of lipid surfaces in the biologicprocessing of adsorbed fibrin(ogen). Dr. Retzinger's laboratory is now exploiting information derived from the study of these model systems to: 1) prepare a platelet analogue for use as a hemostatic agent, 2) develop an adjuvant for general use with vaccines, 3) formulate a method for delivering drugs to formed clots, and 4) inhibit tumor cell metastasis.

Recent Publications

Thacker RI, Retzinger GS. Adsorbed fibrinogen regulates the behavior of human dendritic cells in a CD18-dependent manner. Exp Mol Pathol. 2008Apr;84(2):122-30. Epub 2008 Jan 26. PubMed PMID: 18316072.

Retzinger GS, Takayama K. Mitogenicity of a spread film of monophosphoryllipid A. Exp Mol Pathol. 2005 Oct;79(2):161-7. PubMed PMID: 16054128. 

Einhaus CM, Retzinger AC, Perrotta AO, Dentler MD, Jakate AS, Desai PB,Retzinger GS. Fibrinogen-coated droplets of olive oil for delivery of docetaxelto a fibrin(ogen)-rich ascites form of a murine mammary tumor. Clin Cancer Res.2004 Oct 15;10(20):7001-10. PubMed PMID: 15501980. 

Retzinger GS. Fibrinogen-coated chylomicrons in gastrointestinal lymph: a new rationale regarding the arterial deposition of postprandial lipids. MedHypotheses. 2002 Dec;59(6):718-26. PubMed PMID: 12445516. 

DeAnglis AP, Einhaus CM, Sombun AD, Ee LC, Retzinger GS. Fibrinogen in ratgastrointestinal lymph before, during and after intraduodenal administration ofemulsified triglyceride: fibrinogen bound to chylomicrons in gastrointestinallymph is functional. Thromb Res. 2002 Mar 1;105(5):419-32. PubMed PMID: 12062544.

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