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Marinobufagenin Induced Uremic Cardiomyopathy: The Role of Passive Immunization, Rapamycin, and CD40 Signaling in The Generation of Renal Fibrosis

Haller, Steven T.
http://rave.ohiolink.edu/etdc/view?acc_num=mco1339092544

Abstract Details

2012, Doctor of Philosophy (PhD), University of Toledo, College of Medicine.
Cardiotonic steroids such as marinobufagenin (MBG) and ouabain are specific ligands for the Na/K-ATPase and represent a relatively new class of steroid hormones. Uremic cardiomyopathy is characterized by a decrease in diastolic function, left ventricular hypertrophy, oxidant stress, and both cardiac and renal fibrosis. We have shown that MBG, signaling through the Na/K-ATPase, causes many of the adverse pathological effects of experimental uremic cardiomyopathy induced by 5/6th nephrectomy (PNx) in the rat. The goal of this dissertation is to describe some of the manipulations we have performed in order to provide potential therapies for the treatment of uremic cariomyopathy. Specifically, we show that treatment with an anti-MBG antibody drastically reduces cardiac fibrosis in PNx animals. Treatment with rapamycin (an mTOR inhibitor) produced similar effects with the added benefit of reducing circulating MBG in these animals. In addition, we show that ischemic renal disease is accompanied with elevated levels of the platelet activation marker soluble CD40 ligand (sCD40L), and its soluble receptor, CD40, may predict outcomes in this disease state. Data in our PNx model suggests a role for proximal tubular CD40 activation contributing to the development of renal fibrosis, which may be potentiated by cardiotonic steroid signaling through the Na/K-ATPase.
Joseph Shapiro, MD (Committee Chair)
Christopher Cooper, MD (Committee Member)
Deepak Malhotra, MD, PhD (Committee Member)
Zijian Xie, PhD (Committee Member)
Jiang Liu, PhD (Committee Member)
124 p.
Biomedical Research
cardiotonic steroids; chronic renal failure; ischemic renal disease; CD40; fibrosis

Recommended Citations

Citations

  • Haller, S. T. (2012). Marinobufagenin Induced Uremic Cardiomyopathy: The Role of Passive Immunization, Rapamycin, and CD40 Signaling in The Generation of Renal Fibrosis [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1339092544

    APA Style (7th edition)

  • Haller, Steven. Marinobufagenin Induced Uremic Cardiomyopathy: The Role of Passive Immunization, Rapamycin, and CD40 Signaling in The Generation of Renal Fibrosis. 2012. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1339092544.

    MLA Style (8th edition)

  • Haller, Steven. "Marinobufagenin Induced Uremic Cardiomyopathy: The Role of Passive Immunization, Rapamycin, and CD40 Signaling in The Generation of Renal Fibrosis." Doctoral dissertation, University of Toledo, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=mco1339092544

    Chicago Manual of Style (17th edition)

mco1339092544
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© 2012, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.