拉斯维加斯赌城

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  7. The role of the immune system in hypertension

The role of the immune system in hypertension

Hypertension is the primary contributor to cardiovascular disease, and the leading single contributor to all-cause mortality and disability worldwide. Despite apparent involvement of the immune system in hypertension, no feasible immune-based strategy to control blood pressure and associated target organ inflammation has yet emerged. This is due to our fragmented understanding of how hypertension links to specific immune activation. We and others have demonstrated that the bioactive phospholipid sphingosine-1-phosphate (S1P) critically contributes to disease mechanisms relevant to hypertension, atherosclerosis, heart failure, and stroke. We linked increments in plasma S1P to increasing systolic blood pressure and confirmed in experimental models an essential contribution of the S1P signaling axis to disease initiation.?

?Schematic representation of SphK2-modulated immune and vascular responses to angiotensin II (AngII). AngII mediates the migration of T cells from lymphoid tissues into the blood by increasing the production of S1P through activation of SphK2 in platelets and/or erythrocytes. This increases the plasma concentration of S1P. The inhibition of SphK2 in hematopoietic cells has a decisive influence on the production of S1P in plasma and thus on the generation of an S1P gradient, which is necessary for the migration of T cells. Elevated AngII and S1P levels activate the endothelium of the mesenteric arteries and induce the expression of proinflammatory cytokines and molecules responsible for T cell adhesion. This allows T cells to invade the tissue and accumulate in the vessel wall. The resulting vascular inflammation leads to structural changes with negative effects on vascular reactivity and thus on blood pressure regulation. Adapted from Meissner et al. Cardiovascular Research (2017) 113, 123–133. https://doi.org/10.1093/cvr/cvw256.

Related Funding

Wenner Gren Stiftelse: Immunomodulation in hypertension improves outcome after myocardial infarction - funding period 2022 – 2024

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?ke Wiberg Stiftelse: S1P signaling as new therapeutic target for mechanism-based therapy in hypertension – funding period 2018 – 2020

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Vetenskapsr?det: Communication between Sphingosine-1-phosphate signaling and the Renin-Angiotensin System during hypertension: a bearer of therapeutic significance in blood pressure regulation and Target Organ Damage -?Funding period 2018 - 2020

Related Publications

Jujic Amra, Matthes Frank, Vanherle Lotte, Petzka Henning, Orho-Melander Marju, Nilsson Peter M., Magnusson Martin, Meissner Anja. Plasma S1P (Sphingosine-1-Phosphate) links to hypertension and biomarkers of inflammation and cardiovascular disease: findings from a translational investigation. Hypertension 2021;78(1):195-209. https://doi.org/10.1161/hypertensionaha.120.17379
BibTeX | RIS | DOI
Don‐Doncow Nicholas, Zhang Yun, Matuskova Hana, Meissner Anja. The emerging alliance of sphingosine‐1‐phosphate signalling and immune cells: from basic mechanisms to implications in hypertension. British Journal of Pharmacology 2018;176(12):1989-2001. https://doi.org/10.1111/bph.14381
BibTeX | RIS | DOI
Don-Doncow Nicholas, Vanherle Lotte, Zhang Yun, Meissner Anja. T-Cell accumulation in the hypertensive brain: a role for sphingosine-1-phosphate-mediated chemotaxis. International Journal of Molecular Sciences 2019;20(3):537. https://doi.org/10.3390/ijms20030537
PDF | BibTeX | RIS | DOI
Meissner Anja, Miro Francesc, Jiménez-Altayó Francesc, Jurado Andrés, Vila Elisabet, Planas Anna M.. Sphingosine-1-phosphate signalling—a key player in the pathogenesis of Angiotensin II-induced hypertension. Cardiovascular Research 2017;113(2):123-133. https://doi.org/10.1093/cvr/cvw256
BibTeX | RIS | DOI
Vanherle Lotte, Matthes Frank, Meissner Anja. Targeting sphingosine-1-phosphate signaling in hypertension - a new treatment opportunity [Abstract]. Journal of Vascular Research 2023;60(Supplement 1):16-17. https://doi.org/10.1159/000533846
BibTeX | RIS | DOI

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