Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension

Batchu, Sri Nagarjun; Hughson, Angie; Wadosky, Kristine M.; Morrell, Craig N.; Fowell, Deborah J.; Korshunov, Vyacheslav A.

doi:10.1161/atvbaha.116.307848

Cited by 17 publications

(22 citation statements)

References 39 publications

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“…The data indicated that Axl-expressing immune cells drove pro-inflammatory gene expression and increased immune cell infiltration in the kidney at early stages of hypertension and that Axl expression in both immune and vascular cells was detrimental in the later phases of hypertensive disease. Continuing on from this, the same group demonstrated that Axl is critical for survival of T lymphocytes, affecting vascular remodelling and inflammation in DOCA-salt induced hypertension 107 …”

Section: Axl In Cvdmentioning

confidence: 81%

TAM receptors in cardiovascular disease

McShane

Tabas

Lemke

et al. 2019

Cardiovascular Research

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The TAM receptors are a distinct family of three receptor tyrosine kinases, namely Tyro3, Axl, and MerTK. Since their discovery in the early 1990s, they have been studied for their ability to influence numerous diseases, including cancer, chronic inflammatory and autoimmune disorders, and cardiovascular diseases. The TAM receptors demonstrate an ability to influence multiple aspects of cardiovascular pathology via their diverse effects on cells of both the vasculature and the immune system. In this review, we will explore the various functions of the TAM receptors and how they influence cardiovascular disease through regulation of vascular remodelling, efferocytosis and inflammation. Based on this information, we will suggest areas in which further research is required and identify potential targets for therapeutic intervention.

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Section: Axl In Cvdmentioning

confidence: 81%

TAM receptors in cardiovascular disease

McShane

Tabas

Lemke

et al. 2019

Cardiovascular Research

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“…However, SBP and PP were not significantly different in Axl -/- aging mice compared to WT aging mice with or without testosterone treatment. Korshunov VA [ 35 ] and Batchu N [ 36 ] found Axl deficiency could reduce SBP level in deoxycorticosterone acetate (DOCA)-salt hypertension model, and gas6/Axl contributes to vascular endothelial dysfunction, and remodeling via inhibiting vascular apoptosis, in the late phase of DOCA-salt hypertension. The role of Gas6/Axl on hypertension needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway

Chen

Zhou

Chen

et al. 2020

Aging

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Low serum testosterone level is associated with aging-related vascular stiffness, but the underlying mechanism is unclear. The Growth arrest-specific protein 6 (Gas6) /Axl pathway has been proved to play important roles in cell senescence. In this study, we intend to explore whether Gas6/Axl is involved in the effect of testosterone on vascular aging amelioration. Vascular aging models of wild type and Axl -/- mice were established by natural aging. Mice of these two gene types were randomized into young group, aging group and testosterone undecanoate (TU) treatment group. Mice were treated with TU (37.9 mg/kg) in the TU group, which treated with solvent reagent served as control. The aging mice exhibited decreases in serum testosterone, Gas6 and Axl levels and an increase in cell senescence, manifested age-related vascular remodeling. Testosterone treatment induced testosterone and Gas6 levels in serum, and ameliorated cell senescence and vascular remodeling in aging mice. Furthermore, we uncover the underlying molecular mechanism and show that testosterone treatment restored the phosphorylation of Akt and FoxO1a. Axl knockout accelerated cell senescence and vascular remodeling, and resisted the anti-aging effect of testosterone. Testosterone might exert a protective effect on vascular aging by improving cell senescence and vascular remodeling through the Gas6/Axl pathway.

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“…Thus, this loss in resistance to the pressor effects of Ang II could be due to a spontaneous mutation(s) that makes the T-cell deficient B6.Rag1 −/− -M no longer a model of Ang II-resistant hypertension. While these findings may call into question the physiological importance of T-cells in Ang II-dependent hypertension, a study by Batchu et al 24 using the same Jackson Laboratory strain of B6.Rag1 −/− -M showed that B6.Rag1 −/− -M were resistant to DOCA-salt-induced hypertension. The SBP increased by only 4 mm Hg in B6.Rag1 −/− -M compared to 21 mm Hg in B6.WT-M or to 19 mm Hg in CD3➔B6.Rag1-M. Taken together, these findings raise the possibility that T-cell modulation of blood pressure may be more dependent on sodium than Ang II in B6.Rag1 −/− -M.…”

Section: Discussionmentioning

confidence: 99%

Loss of Resistance to Angiotensin II–Induced Hypertension in the Jackson Laboratory Recombination-Activating Gene Null Mouse on the C57BL/6J Background

Pai

West³

et al. 2017

Hypertension

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Resistance to angiotensin II (Ang II)-induced hypertension in T-cell deficient male mice with a targeted mutation in the recombination activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1−/−-M), which was reported by five independent laboratories including ours prior to 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure (MAP) induced by two weeks of Ang II infusion at 490 ng/kg/min was identical between B6.Rag1−/−-M and wildtype littermates (B6.WT-M). Moreover, there were no differences in the time course or magnitude increase in MAP at the lowest dose of Ang II (200 ng/kg/min) that increased MAP. This loss in Ang II resistance is independent of T-cells. Angiotensin-type1-receptor (AT1R) binding was 1.4-fold higher in glomeruli isolated from recently purchased B6.Rag1−/−-M suggesting an increase in renal AT1R activity masks the blood pressure protection afforded by the lack of T-cells. The phenotypic change in B6.Rag1−/−-M has implications for investigators using this strain to study mechanisms of T-cell modulation of Ang II-dependent blood pressure control. These findings also serve as a reminder that the universal drive for genetic variation occurs in all animals including inbred mouse strains and that spontaneous mutations leading to phenotypic change can compromise experimental reproducibility over time and place. Lastly, these observations illustrate the importance of including experimental details regarding the location and time period over which animals are bred in publications involving animal studies to promote rigor and reproducibility in the scientific literature.

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Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension

Cited by 17 publications

References 39 publications

TAM receptors in cardiovascular disease

TAM receptors in cardiovascular disease

Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway

Loss of Resistance to Angiotensin II–Induced Hypertension in the Jackson Laboratory Recombination-Activating Gene Null Mouse on the C57BL/6J Background

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