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Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2018 Jan; Vol. 71 (1), pp. 199-207. Date of Electronic Publication: 2017 Nov 13. - Publication Year :
- 2018
-
Abstract
- The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA.<br /> (© 2017 American Heart Association, Inc.)
- Subjects :
- Animals
Biological Factors administration & dosage
Blood Pressure drug effects
Calcineurin Inhibitors adverse effects
Calcineurin Inhibitors pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Kidney drug effects
Kidney metabolism
Mice
Blood Vessels drug effects
Blood Vessels metabolism
Cyclosporine adverse effects
Cyclosporine pharmacology
Hypertension chemically induced
Hypertension metabolism
Hypertension prevention & control
Interleukin-33 administration & dosage
Myeloid-Derived Suppressor Cells drug effects
Myeloid-Derived Suppressor Cells physiology
Renal Insufficiency chemically induced
Renal Insufficiency prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 71
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 29133357
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.117.10306