DOI

https://doi.org/10.25772/6M9G-W703

Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Stefano Toldo

Second Advisor

Antonio Abbate

Third Advisor

Roland Pittman

Abstract

Background: Heart Failure (HF) is characterized by impaired cardiac function with symptoms of dyspnea, fatigue and exercise intolerance. Western diet (WD), a diet high in saturated fats and sugars, causes systemic increase in IL-18, a cytokine elevated in HF, which induces abnormal myocardial structure and diastolic dysfunction. IL-18 binding protein(IL-18BP) binds IL-18, preventing the binding to the IL-18-receptor. We investigated a therapeutic intervention using recombinant-murine IL-18BP to improve the WD-induced cardiomyopathy in C57BL/6J mice.

Methods: Echocardiography with pulse-wave Doppler and tissue imaging was performed to assess cardiac function. Oral glucose tolerance test was performed to assess metabolic parameters and IL-18 plasma levels were quantified with ELISA.

Results: WD-fed mice had worsened isovolumetric relaxation time (IVRT) and myocardial performance index (MPI), indicating cardiac dysfunction. Daily intraperitoneal injections of 0.5mg/kg IL-18BP for two weeks, significantly improved both IVRT and MPI.

Conclusions: IL-18BP treatment improves cardiac function in a model of WD-induced cardiomyopathy.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-2-2017

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