RRC ID 168
Author Li PG, Xu JW, Ikeda K, Kobayakawa A, Kayano Y, Mitani T, Ikami T, Yamori Y.
Title Caffeic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II in stroke-prone spontaneously hypertensive rats.
Journal Hypertens Res
Abstract Epidemiological studies have linked the consumption of phenolic acids with reduced risk of cardiovascular diseases. In the present study, we sought to investigate whether caffeic acid, a phenolic acid which is abundant in normal diet, can antagonize angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats, and if so, to elucidate the underlying cell signaling mechanisms. We exposed VSMCs to Ang II and caffeic acid and found that caffeic acid significantly inhibited intracellular superoxide anion generation (decreased from 127 +/- 6.3% to 100.3 +/- 6.6% of the control cells) and the cell proliferation induced by Ang II. Furthermore, caffeic acid significantly abolished the tyrosine phosphorylation of JAK2 (decreased from 7.4 +/- 0.6-fold to 2.4 +/- 0.6-fold at 2 min) and STAT1 (decreased from 1.8 +/- 0.2-fold to 0.5 +/- 0.1-fold at 2 min) and the phosphorylation of ERK1/2 (decreased from 99.2 +/- 10.2-fold to 49.8 +/- 10.9-fold at 2 min) that were induced by Ang II. These effects of caffeic acid were consistent with the inhibition of the proliferation of VSMCs by DPI, an NADPH oxidase inhibitor, and by AG-490, a JAK2 inhibitor. In conclusion, our findings suggest that caffeic acid attenuates the proliferative reaction of VSMCs to Ang II stimulation in both SHRSP and WKY rats by inhibiting the generation of reactive oxygen species and then partially blocking the JAK/STAT signaling cascade and the Ras/Raf-1/ERK1/2 cascade.
Volume 28(4)
Pages 369-77
Published 2005-4-1
DOI 10.1291/hypres.28.369
PMID 16138568
MeSH Angiotensin II / pharmacology* Animals Antioxidants / pharmacology* Caffeic Acids / pharmacology* Cell Division / drug effects DNA-Binding Proteins / metabolism Drug Interactions Enzyme Inhibitors / pharmacology HSP90 Heat-Shock Proteins / metabolism Hypertension / chemically induced Hypertension / drug therapy* Janus Kinase 2 Male Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Muscle, Smooth, Vascular / cytology Muscle, Smooth, Vascular / drug effects* Muscle, Smooth, Vascular / metabolism Phosphorylation / drug effects Protein-Tyrosine Kinases / antagonists & inhibitors Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins / antagonists & inhibitors Proto-Oncogene Proteins / metabolism Rats Rats, Inbred SHR Rats, Inbred WKY STAT1 Transcription Factor Signal Transduction / drug effects Stroke / prevention & control Superoxides / metabolism Trans-Activators / metabolism Tyrosine / metabolism Tyrphostins / pharmacology Vasoconstrictor Agents / pharmacology*
IF 2.941
Times Cited 42
Rats SHRSP/Izm(strainID=409) WKY/Izm(strainID=412)