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 2019 Jun

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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. PGG was administered to mice every 2 days at a dose of 10 mg·kg-1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 μM for in vitro studies in cultured cells. 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. 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 monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) 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 the BP increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T-cells. It also decreased the content of IFN-γ+ CD8+ and CD3+ CD4- CD8- cells and IL-17A+ CD3+ CD4- CD8- cells. PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc. © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Citation

Tomasz P Mikolajczyk, Ryszard Nosalski, Dominik S Skiba, Joanna Koziol, Magdalena Mazur, Amauri S Justo-Junior, Paulina Kowalczyk, Zofia Kusmierczyk, Agata Schramm-Luc, Kevin Luc, Pasquale Maffia, Delyth Graham, Anna K Kiss, Marek Naruszewicz, Tomasz J Guzik. 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. 2019 Jun;176(12):1951-1965