| First Author | Mikolajczyk TP | Year | 2019 |
| Journal | Br J Pharmacol | Volume | 176 |
| Issue | 12 | Pages | 1951-1965 |
| PubMed ID | 30658013 | Mgi Jnum | J:278905 |
| Mgi Id | MGI:6359248 | Doi | 10.1111/bph.14583 |
| Citation | Mikolajczyk TP, et al. (2019) 1,2,3,4,6-Penta-O-galloyl-beta-d-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension. Br J Pharmacol 176(12):1951-1965 |
| abstractText | 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-beta-d-glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. EXPERIMENTAL APPROACH: 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 muM for in vitro studies in cultured cells. 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. 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-gamma(+) 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 muM) directly inhibited CD25 and CCR5 expression in cultured T-cells. It also decreased the content of IFN-gamma(+) CD8(+) and CD3(+) CD4(-) CD8(-) cells and IL-17A(+) CD3(+) CD4(-) CD8(-) cells. CONCLUSION AND IMPLICATION: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. LINKED ARTICLES: 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. |
