Document Type

Dissertation - Open Access

Award Date


Degree Name

Doctor of Philosophy (PhD)

Department / School

Pharmaceutical Sciences

First Advisor

Omathanu Perumal


Cardiac dysfunction, cardiac fibrosis, diabetic cardiomyopathy, fingolimod, sphingosine 1-phosphate receptor 1 (S1P1), T cell trafficking


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


Includes bibliographical references (page 190-212)



Number of Pages



South Dakota State University



Rights Statement

In Copyright