1,2,3,4,6 penta-O -galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension.

Mikolajczyk, T. P. et al. (2019) 1,2,3,4,6 penta-O -galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension. British Journal of Pharmacology, 176(12), pp. 1951-1965. (doi:10.1111/bph.14583) (PMID:30658013)

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Abstract

Background and Purpose: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental Approach: PGG was administered every two days in a dose of 10 mg·kg‐1 i.p during 14‐days of Ang II infusion and was used in a final concentration of 20 μM for in vitro studies. Key Results: Ang II administration increased leukocyte and T cell content in perivascular adipose tissue (pVAT) and administration of PGG significantly decreased total leukocyte and T cell infiltration in pVAT (1640±150 vs. 1028±57, p<0.01; 321±22 vs 158±18, cells/mg; p<0.01, respectively). This effect was observed in relation to all T cell subsets. PGG also decreased the content of T cells bearing CD25, CCR5 and CD44 receptors and the expression of both MCP‐1 in aorta and RANTES in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T cells and IL‐17A+ CD4+ and CD3+CD4‐CD8‐ cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of blood pressure increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T cells. It also decreased the content of IFN‐γ+ by CD8+ and CD3+CD4‐CD8‐ cells and IL‐17A+ by CD3+CD4‐CD8‐ cells. Conclusion and Implication: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension.

Item Type:Articles
Additional Information:This study was supported by the Wellcome Trust [International Senior Research Fellowship to TJG], European Commission Marie Curie CIG (Nr 631773), European Research Council (InflammaTENSION); British Heart Foundation Centre for Excellence [RE/13/5/30177]; Polish National Science Center grant (2013/09/N/NZ4/02211- MM) and the Mobility Plus Program of Polish Ministry of Science and Higher Education (1280/MOB/IV/2015/0 - TPM) and (1300/1/MOB/IV/2015/0 - DS).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nosalski, Mr Ryszard and Maffia, Dr Pasquale and Skiba, Mr Dominik and Mikolajczyk, Dr Tomasz and Guzik, Professor Tomasz and Graham, Dr Delyth and Justo Junior, Amauri
Authors: Mikolajczyk, T. P., Nosalski, R., Skiba, D. S., Koziol, J., Mazur, M., Justo Junior, A. S., Kowalczyk, P., Kusmierczyk, Z., Schramm Luc, A., Luc, K., Maffia, P., Graham, D., Kiss, A. K., Naruszewicz, M., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:British Journal of Pharmacology
Publisher:John Wiley & Sons, Inc.
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:18 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in British Journal of Pharmacology 176:1951-1965
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
651771ImmunoTensionTomasz GuzikEuropean Commission (EC)631773RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES

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