Genistein affects the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells.
BACKGROUND
Several lines of evidence suggest that the dietary isoflavone genistein (Gen) has beneficial effects with regard to cardiovascular disease and in particular on aspects related to blood pressure and angiogenesis. The biological action of Gen may be, at least in part, attributed to its ability to affect cell signalling and response. However, so far, most of the molecular mechanisms underlying the activity of Gen in the endothelium are unknown.


RESULTS
To examine the transcriptional response to 2.5 microM Gen on primary human endothelial cells (HUVEC), we applied cDNA array technology both under baseline condition and after treatment with the pro-atherogenic stimulus, copper-oxidized LDL. The alteration of the expression patterns of individual transcripts was substantiated using either RT-PCR or Northern blotting. Gen significantly affected the expression of genes encoding for proteins centrally involved in the vascular tone such as endothelin-converting enzyme-1, endothelin-2, estrogen related receptor alpha and atrial natriuretic peptide receptor A precursor. Furthermore, Gen countered the effect of oxLDL on mRNA levels encoding for vascular endothelial growth factor receptor 165, types 1 and 2.


CONCLUSIONS
Our data indicate that physiologically achievable levels of Gen change the expression of mRNA encoding for proteins involved in the control of blood pressure under baseline conditions and reduce the angiogenic response to oxLDL in the endothelium.
Ambra
R
R
National Institute for Food and Nutrition Research, via Ardeatina 546, I-00178 Rome, Italy.
Rimbach
G
G
de Pascual Teresa
S
S
Fuchs
D
D
Wenzel
U
U
Daniel
H
H
Virgili
F
F
D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D019833:Genistein