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Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats
Joint Authors
Luck, Christian
DeMarco, Vincent G.
Mahmood, Abuzar
Gavini, Madhavi P.
Pulakat, Lakshmi
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-03-20
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Diabetes is comorbid with cardiovascular disease and impaired immunity.
Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1).
However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity.
Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats.
Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose.
Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt.
Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL.
Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO.
Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.
American Psychological Association (APA)
Luck, Christian& DeMarco, Vincent G.& Mahmood, Abuzar& Gavini, Madhavi P.& Pulakat, Lakshmi. 2017. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-17.
https://search.emarefa.net/detail/BIM-1195030
Modern Language Association (MLA)
Luck, Christian…[et al.]. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-17.
https://search.emarefa.net/detail/BIM-1195030
American Medical Association (AMA)
Luck, Christian& DeMarco, Vincent G.& Mahmood, Abuzar& Gavini, Madhavi P.& Pulakat, Lakshmi. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-17.
https://search.emarefa.net/detail/BIM-1195030
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195030