Document Type
Dissertation - Open Access
Award Date
2016
Degree Name
Doctor of Philosophy (PhD)
Department / School
Pharmaceutical Sciences
First Advisor
Omathanu Perumal
Keywords
Cardiac dysfunction, cardiac fibrosis, diabetic cardiomyopathy, fingolimod, sphingosine 1-phosphate receptor 1 (S1P1), T cell trafficking
Abstract
Diabetic cardiomyopathy is a distinct pathological condition characterized by myocardial fibrosis and cardiac dysfunction in diabetic patients. The resolution of myocardial fibrosis to improve cardiac function in diabetes is an active area of research. Notably, increased T lymphocyte infiltration into myocardium has been attributed to increased cardiac fibrosis and dysfunction in diabetes. However, the experimental data on the role of T lymphocyte modulation in diabetic myocardial fibrosis is scarce. To this end, sphingosine 1-phosphate receptor 1 (S1P1) regulates the egress of mature T lymphocytes from lymphoid organs to blood and peripheral organs. Thus, the inhibition of T cells trafficking through S1P1 receptor modulation is a potential translational approach to protect the heart in diabetes. We hypothesized that inhibition of T lymphocyte trafficking by modulating S1P1 receptor protects diabetic heart and ameliorates fibrosis. To accomplish this overarching objective, we conducted three related studies: (1) assess the effects of fingolimod (S1P1 receptor modulator) treatment in diabetes-induced myocardial fibrosis in mice; (2) study cardiac fibrosis and dysfunction in diabetes using conditional T-cell S1P1 knockout (TS1P1KO) mice; (3) evaluate the effects of CD4+ T cells transfer to TS1P1KO mice in diabetes-induced myocardial fibrosis and dysfunction.
Library of Congress Subject Headings
Diabetic cardiomyopathies
Myocardium -- Diseases
Diabetes -- Complications
T cells
Lymphocytes
Description
Includes bibliographical references (page 190-212)
Format
application/pdf
Number of Pages
en
Publisher
South Dakota State University
Recommended Citation
Abdullah, Chowdhury Sayef, "Role of T Lymphocyte Trafficking in Diabetic Cardiomyopathy" (2016). Electronic Theses and Dissertations. 965.
https://openprairie.sdstate.edu/etd/965
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