In:
Pharmacology, S. Karger AG, Vol. 99, No. 5-6 ( 2017), p. 291-302
Abstract:
The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs. The DMPQ attenuated monocyte-EC interaction but it did not affect monocyte adhesion to matrix. In parallel, DMPQ reduced tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule and vascular CAM expression in ECs. DMPQ compromised TNF-α-induced I & #x03BA;B activation, nuclear factor-kappa B (NF- & #x03BA;B) translocation, and NF- & #x03BA;B-DNA complex formation. Moreover, it affected TNF-α- and hydrogen peroxide (H 〈 sub 〉 2 〈 /sub 〉 O 〈 sub 〉 2 〈 /sub 〉 )-induced reactive oxygen species production and I & #x03BA;B activation. These suggest that DMPQ affects CAM expression by affecting NF- & #x03BA;B signaling. Meanwhile, DMPQ could also inhibit platelet-derived growth factor (PDGF)-induced VSMC migration toward collagen by affecting cellular PDGF signaling, including PDGFRβ, PLC & #x03B3;, ERK1/2, and Akt phosphorylation. The VSMC adhesion to collagen and collagen-induced focal adhesion kinase activation during cell adhesion were impaired by DMPQ treatment. This study reveals a phenanthrene derivative-DMPQ-with anti-inflammatory and anti-migratory bioactivity toward vascular ECs and SMCs, suggesting its protective effect on vascular injuries.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2017
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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