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Antiangiogenic properties of natural polyphenols from red propolis
Author(s) -
Daleprane Julio Beltrame,
Dehne Nathalie,
Ong Thomas Prates,
Brüne Bernard,
Abdalla Dulcineia Saes Parra
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb236
Subject(s) - angiogenesis , downregulation and upregulation , ldl receptor , chemistry , cancer research , receptor , microbiology and biotechnology , cholesterol , lipoprotein , biology , biochemistry , gene
We investigated the effects of polyphenols from red propolis (PRP) on angiogenesis in atherosclerosis. The LDL receptor gene (LDLr−/−) knockout mice received a cholesterol‐enriched diet and PRP (250mg/Kg/day) by gavage during 4 weeks. Migrations of ECs, ECs sprouting from murine aortic rings, formation of new blood vessels in the chorio‐allantoic chiken embryo (CAM) and differentiation of stem cell (SCs) in CD‐31 positive cells were used as angiogenesis models. PRP decreased atherosclerosis lesion area and expression of inflammatory factors in LDLr−/−. Furthermore, the expression of the pro‐angiogenic factors FGF, VEGF and PECAM was downregulated by PRP. In agiogenesis model PRP (10 μg/ml) inhibited the angiogenic process in all protocols. Specifically, PRP reduced HIF‐1α protein half‐life, from ~58 to ~38 min under hypoxic conditions. The reduced protein half‐life was due to increased von Hippel‐Lindau (pVHL)‐dependent proteasomal degradation of HIF‐1α, which was correlated with PRP‐evoked downregulation of Cdc42 but a subsequent pVHL increase. PRP are atheroprotective through mechanisms including modulation of inflammatory and angiogenic factors mailing modulating HIF‐1α stabilization. FAPESP, grants to D.S.P.A. (08/53756‐7) and Ph.D. scholarship to J.B.D. (08/53755‐0).