Date

July 2012

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Molecular and Medical Genetics

Institution

Oregon Health & Science University

Abstract

The γ’ isoform of fibrinogen is associated with cardiovascular disease (CVD) and may be useful for cardiovascular risk prediction. This isoform is produced through the incorporation of a splice variant of the fibrinogen γ chain into the molecule, and its levels vary between individuals. It has been proposed that γ’ fibrinogen may increase the risk of thrombosis through its interactions with thrombin, the major blood coagulation enzyme. In this dissertation, the role of electrostatic interactions in this binding was investigated using surface plasmon resonance technology. Our findings indicate that the binding of exosite II of thrombin to the γ’ chain is mediated by the ensemble of negatively-charged residues in the γ’ chain carboxyl terminus, and that no single charged residue is absolutely required. As CVD appears to be an inflammatory process, the relationship between γ’ fibrinogen and inflammation was explored in a cohort of subjects from the Periodontitis and Vascular Events (PAVE)

Identifier

doi:10.6083/M4ZS2THV

School

School of Medicine

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