Date of Award

January 2016

Degree Type

Open Access Thesis

Document Type

Master Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

First Advisor

Rebekah L. Waikel

Department Affiliation

Biological Sciences

Second Advisor

Marcia M. Pierce

Department Affiliation

Biological Sciences

Third Advisor

Lindsay E. Calderon

Department Affiliation

Biological Sciences

Abstract

Transforming growth factor beta ligands and receptors are known to be pro-hypertrophic and pro-fibrotic factors in the heart, and are known to contribute to the development of cardiac hypertrophy and heart failure. It is well established that premenopausal females possess a lower incidence of these pathologies. We and others have observed a greater level of fibrosis in male hearts compared to female hearts in rodent models of cardiac hypertrophy. It is well established that estrogen is cardioprotective in that it can prevent the development of cardiac hypertrophy, as well as abrogate the development of heart failure following sustained cardiac hypertrophy. It is not fully understood how estrogen mediates these cardioprotective effects. In this study, we address the hypothesis that sex differences in the development of cardiac hypertrophy and heart failure is at least in part mediated by differential expression of TGFβ family members. To test this hypothesis, we utilized an angiotensin II pump infusion rodent model of cardiac hypertrophy in both male and female mice, followed by gene expression analysis and gene expression analysis of non-failing and failing human heart specimens. Interestingly, sex differences in cardiac hypertrophy were not observed in the angiotensin II pump mouse model, suggesting that angiotensin II may circumvent the cardioprotection afforded to females. Interestingly, TGFβ family members were more similarly expressed in this mouse model. Taken together these results provide evidence that sex specific differences in the development of cardiac hypertrophy are mediated in part by TGFβ signaling. Human hearts reveal some sex differential gene regulation in both non-failing and failing hearts. Taken together, these results provide evidence that sex specific differences in the development of cardiac hypertrophy and heart failure are mediated in part by TGFβ signaling.

Download

Share

COinS