TY - JOUR
T1 - Divergent effects of estrogen and nicotine on Rho-kinase expression in human coronary vascular smooth muscle cells
AU - Hiroki, Junko
AU - Shimokawa, Hiroaki
AU - Mukai, Yasushi
AU - Ichiki, Toshihiro
AU - Takeshita, Akira
N1 - Funding Information:
We thank M. Sonoda, M. Motoishi, and S. Masuda for excellent technical assistance. This study was supported in part by the grant for the 21st Century COE Program and the Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan (Nos. 10177223, 10357006, 12032215, 12470158, 12877114, 13307024, and 13557068) and the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan.
PY - 2004/12/31
Y1 - 2004/12/31
N2 - Recent studies have demonstrated that up-regulated Rho-kinase plays an important role in the pathogenesis of coronary arteriosclerosis and vasospasm. We have shown that inflammatory stimuli, such as angiotensin II and interleukin-1β, up-regulate Rho-kinase expression and activity in human coronary vascular smooth muscle cells, for which intracellular signal transduction mediated by protein kinase C and NF-κB is involved. Here, we show that estrogen down-regulates while nicotine up-regulates Rho-kinase and that nicotine counteracts the inhibitory effect of estrogen on angiotensin II-induced Rho-kinase expression. Furthermore, we demonstrated that the intracellular signal transduction of the inhibitory effect of estrogen is mediated by an estrogen receptor. These results demonstrate that inflammatory stimuli up-regulate Rho-kinase, for which estrogen (mediated by an estrogen receptor) and nicotine exert divergent inhibitory and stimulatory effects on the Rho-kinase expression, respectively, and may explain in part why the incidence of arteriosclerotic and vasospastic disorders is increased in postmenopausal women and smokers.
AB - Recent studies have demonstrated that up-regulated Rho-kinase plays an important role in the pathogenesis of coronary arteriosclerosis and vasospasm. We have shown that inflammatory stimuli, such as angiotensin II and interleukin-1β, up-regulate Rho-kinase expression and activity in human coronary vascular smooth muscle cells, for which intracellular signal transduction mediated by protein kinase C and NF-κB is involved. Here, we show that estrogen down-regulates while nicotine up-regulates Rho-kinase and that nicotine counteracts the inhibitory effect of estrogen on angiotensin II-induced Rho-kinase expression. Furthermore, we demonstrated that the intracellular signal transduction of the inhibitory effect of estrogen is mediated by an estrogen receptor. These results demonstrate that inflammatory stimuli up-regulate Rho-kinase, for which estrogen (mediated by an estrogen receptor) and nicotine exert divergent inhibitory and stimulatory effects on the Rho-kinase expression, respectively, and may explain in part why the incidence of arteriosclerotic and vasospastic disorders is increased in postmenopausal women and smokers.
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U2 - 10.1016/j.bbrc.2004.11.011
DO - 10.1016/j.bbrc.2004.11.011
M3 - Article
C2 - 15567165
AN - SCOPUS:9644257091
SN - 0006-291X
VL - 326
SP - 154
EP - 159
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -