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Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2016 Aug; Vol. 36 (8), pp. 1638-1646. Date of Electronic Publication: 2016 Jun 30. - Publication Year :
- 2016
-
Abstract
- Objective: Survival of immune and nonimmune cells relies on Axl, a receptor tyrosine kinase, which is implicated in hypertension. Activated T lymphocytes are involved in regulation of high blood pressure. The goal of the study was to investigate the role of Axl in T-lymphocyte functions and its contribution to salt-dependent hypertension.<br />Approach and Results: We report increased apoptosis in peripheral blood from Axl(-/-) mice because of lower numbers of white blood cells mostly lymphocytes. In vitro studies showed modest reduction in interferon gamma production in Axl(-/-) type 1 T helper cells. Axl did not affect basic proliferation capacity or production of interleukin 4 in Axl(-/-) type 2 T helper cells. However, competitive repopulation of Axl(-/-) bone marrow or adoptive transfer of Axl(-/-) CD4(+) T cells to Rag1(-/-) mice showed robust effect of Axl on T lymphocyte expansion in vivo. Adoptive transfer of Axl(-/-) CD4(+) T cells was protective in a later phase of deoxycorticosterone-acetate and salt hypertension. Reduced numbers of CD4(+) T cells in circulation and in perivascular adventitia decreased vascular remodeling and increased vascular apoptosis in the late phase of hypertension.<br />Conclusions: These findings suggest that Axl is critical for survival of T lymphocytes, especially during vascular remodeling in hypertension.<br /> (© 2016 American Heart Association, Inc.)
- Subjects :
- Adoptive Transfer
Animals
CD4-Positive T-Lymphocytes pathology
CD4-Positive T-Lymphocytes transplantation
Cell Proliferation
Cell Survival
Cells, Cultured
Desoxycorticosterone Acetate
Disease Models, Animal
Genotype
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Hypertension genetics
Hypertension pathology
Hypertension physiopathology
Interferon-gamma metabolism
Interleukin-4 metabolism
Lymphocyte Activation
Male
Mice, Knockout
Phenotype
Proto-Oncogene Proteins deficiency
Proto-Oncogene Proteins genetics
Receptor Protein-Tyrosine Kinases deficiency
Receptor Protein-Tyrosine Kinases genetics
Signal Transduction
Time Factors
Vascular Remodeling
Axl Receptor Tyrosine Kinase
Apoptosis
Blood Pressure
CD4-Positive T-Lymphocytes enzymology
Hypertension enzymology
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Sodium Chloride, Dietary
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 36
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 27365404
- Full Text :
- https://doi.org/10.1161/ATVBAHA.116.307848