Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. Claudio Martin

Abstract

The disruption of myocardial extracellular matrix (ECM) has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin-33 (IL-33) is a cytokine which regulates collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL-33 contributes to sepsis-induced myocardial dysfunction through regulation of matrix metalloproteinase-9 (MMP-9). The in vivo, feces-induced peritonitis (FIP) in mice and in vitro lipopolysaccharide (LPS) treatments to isolated cardiomyocytes were used. In FIP mice, myocardial IL-33 and MMP-9 expression were increased and myocardial contractility was decreased. Myocardial function in FIP mice was improved when treated with soluble ST2 (sST2), a decoy receptor of IL-33. The in vitro expression of IL-33 and MMP-9 in LPS-treated cardiomyocytes was increased. Addition of sST2 prevented the increase of MMP-9 expression in LPS-treated cardiomyocytes. Our results support that IL-33 plays an important role in mediating sepsis-induced myocardial dysfunction.

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