© 1997 American Heart Association, Inc.
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Effects of Estrus Cycle, Ovariectomy, and Treatment with Estrogen, Tamoxifen, and Progesterone on Apolipoprotein(a) Gene Expression in Transgenic Mice
From the Falk Cardiovascular Research Center, Stanford University School of Medicine, Palo Alto, Calif (B.R.Z., R.M.L.) and Cardiovascular Department, Berlex Biosciences, Richmond, Calif (K.K., G.M.R.).
Correspondence to Gabor M. Rubanyi, MD, PhD, Cardiovascular Department, Berlex Biosciences, 15049 San Pablo Ave., Richmond, CA 94804-0099.
Abstract Plasma levels of lipoprotein(a) (Lp(a)), are regulated by the synthetic rate of apolipoprotein(a) (apo(a)), a major protein component of this atherogenic lipoprotein. Exogenously administered sex steroid hormones are potent regulators of plasma Lp(a) concentrations. We utilized a recently developed apo(a) yeast artificial chromosome (YAC) transgenic mouse model to study the effects of ovariectomy, estrus cycle, and exogenous administration of ethinyl-estradiol, the partial estrogen receptor agonist, tamoxifen, and progesterone on circulating apo(a) plasma levels. Analysis of liver RNA revealed that estrogen and tamoxifen exerts their plasma apo(a) lowering effect at the level of apo(a) mRNA. This action of estrogen and tamoxifen may contribute to their antiatherosclerotic and cardiovascular protective effect.
Key Words: apolipoprotein(a) • gene regulation • estrogen • lipoprotein(a) • atherosclerosis
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