Divergent effects of estrogen and nicotine on Rho-kinase expression in human coronary vascular smooth muscle cells.
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-1beta, 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-kappaB 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.
Hiroki
Junko
J
Department of Cardiovascular Medicine, The 21st Century COE Program on Lifestyle-Related Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Shimokawa
Hiroaki
H
Mukai
Yasushi
Y
Ichiki
Toshihiro
T
Takeshita
Akira
A
D000804:Angiotensin II / Q000494:pharmacology; D002460:Cell Line; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D054460:rho-Associated Kinases
D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; D000804:Angiotensin II; D009538:Nicotine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases