ABSTRACT
Elevated levels of plasma lipoprotein(a) (Lp(a))is considered an independent risk factor for coronary heart disease. Lp(a) consists of two apolipoproteins, such as the LDL particle apoB-100 and apo(a), which is unique for Lp(a). Circulating levels of Lp(a) is determined by the synthetic rate of apo(a), rather than its degradation. Sexual steroid hormones have been suggested to be potent regulators of circulating Lp(a), which is highly resistant to conventional lipid lowering therapies. Vasculoprotection by estrogen possibly includes the effect of the hormone on plasma lipids. Lp(a) lowering effect of estrogen has been demonstrated in response to endogenous or exogenously applied hormones. In recent studies from our laboratory we have investigated the mechanism of action of estrogen on apo(a) levels utilizing the YAC apo(a) transgenic mice, in which liver expression of apo(a) is driven by the human promoter. We found that hormonal changes during the estrus cycle of these mice affected circulating apo(a) levels, suggesting that this model is useful to study the regulation of apo(a). Our results with exogenously applied estrogens suggest that the Lp(a) lowering effect of the hormone is likely mediated by decreased mRNA expression of apo(a) in the liver of the transgenic animals.
