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1. Harper, Shavonn Christine. The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy.
Degree: PhD, 2018, Temple University
Pathological cardiac hypertrophy (PCH) occurs in response to pathological stimuli affecting the heart such as coronary artery disease, myocardial infarction, or hypertension. PCH is also be independent risk factor for cardiac events and/or sudden death. Despite therapeutic advancements in the treatment of cardiovascular diseases (CVD) and heart failure, deaths due to CVD remain the leading cause of mortality worldwide. Furthermore, treatment of these cardiovascular diseases slows their progression, but individuals eventually progress to heart failure, which has a 5-year survival rate of approximately 50 percent. There is a clear need for development of new therapies that can reverse PCH and the associated damage to the heart. As healthcare improves, populations are living longer, and illness due to age increases. One issue that occurs with aging is loss of normal cardiac function leading to heart failure. This functional decline is accompanied by morphological changes in the heart, including hypertrophy. Although it is well documented that myocardial remodeling occurs with aging, the mechanisms underlying these changes are poorly understood. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGF-β) superfamily of proteins, which regulate a number of cellular processes. Shared circulation of a young mouse with an old mouse or a single daily intraperitoneal (IP) injection of GDF11 for 30 days was shown to reverse aging-induced pathological cardiac hypertrophy. This molecule is highly homologous with another TGF-β family member, myostatin, which is a known negative growth regulator of skeletal muscle. We began by attempting to validate published data claiming that a single daily intraperitoneal (IP) injection of 0.1 mg/kg/day of GDF11 could reverse aging induced cardiac hypertrophy. We performed a blinded study during which treated 24-month-old C57BL/6 male mice with a single IP injection of 0.1 mg/kg/day of GDF11for 28 days and monitored changes in cardiac function and structure using echocardiography (ECHO). We also looked for differences in fibrosis, myocyte size, markers of pathological hypertrophy and heart weight. We were unable to find any differences between vehicle treated age mice and GDF11 treated aged mice in any of the measured parameters. While we did find an increase in heart weight between 8-week-old mice and the 24-month-old mice, there was no difference in the heart weight to body weight ratios of these groups of animals. From these data we concluded that our aged- mice did not have pathological hypertrophy and the dose of GDF11 used in this study did not have any effect on cardiac structure or function. Hypertensive heart disease results in changes in cardiac structure and function including left ventricular hypertrophy, systolic and/or diastolic dysfunction. It is also a leading cause of heart failure. Members of the TGF-β superfamily of proteins have been shown to be involved in many of the processes that occur in the heart in response to…Advisors/Committee Members: Houser, Steven R.;, Autieri, Michael V., Franti, Michael, Koch, Walter J., Mohsin, Sadia;.
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APA (6th Edition):
Harper, S. C. (2018). The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,498061
Chicago Manual of Style (16th Edition):
Harper, Shavonn Christine. “The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy.” 2018. Doctoral Dissertation, Temple University. Accessed July 02, 2020. http://digital.library.temple.edu/u?/p245801coll10,498061.
MLA Handbook (7th Edition):
Harper, Shavonn Christine. “The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy.” 2018. Web. 02 Jul 2020.
Harper SC. The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy. [Internet] [Doctoral dissertation]. Temple University; 2018. [cited 2020 Jul 02]. Available from: http://digital.library.temple.edu/u?/p245801coll10,498061.
Council of Science Editors:
Harper SC. The Effects of Growth Differentiation Factor 11 on Pathological Cardiac Hypertrophy. [Doctoral Dissertation]. Temple University; 2018. Available from: http://digital.library.temple.edu/u?/p245801coll10,498061