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Abstract
BackgroundAn inverse relationship between the level of high-density lipoprotein (HDL) and coronary heart disease (CHD) has been reported. In contrast, oxidized HDL (oHDL) has been shown to induce neuronal death and may play an important role in the pathogenesis of CHD. In the present study we have investigated a: the effect of various equine estrogens on HDL oxidation, b: the inhibition of LDL oxidation by HDL and c: the effect of these estrogens on LDL oxidation in the presence of HDL.ResultsAll 11 equine estrogens tested protected the HDL from oxidation in a concentration dependant manner. Equilenin, 17β-dihydroequilenin, and 17α-dihydroequilenin (Δ6–8-estrogens) were found to be the most potent inhibitors of HDL oxidation. Some of the novel ring B unsaturated estrogens were 2.5 to 4 times more potent inhibitors of HDL oxidation than 17β-estradiol. HDL was found to delay LDL oxidation. The protection of LDL oxidation by HDL is enhanced by the addition of estrogen, with equilenin being again more potent than 17β-estradiol.ConclusionsEquine estrogens can differentially inhibit the oxidation of HDL with the Δ6–8-estrogens being the most potent antioxidants. The ability of estrogens to enhance HDL's antioxidant activity is to our knowledge the first report of an interaction of estrogen with HDL that results in the delay or inhibition of LDL oxidation. This may be another mechanism by which estrogens may reduce the risk of CHD and neurodegenerative diseases in healthy and younger postmenopausal women.
Highlights
An inverse relationship between the level of high-density lipoprotein (HDL) and coronary heart disease (CHD) has been reported
Epidemiological data has suggested a strong inverse correlation between plasma HDL concentrations and the incidence of coronary and cerebral atherosclerosis [9,10]. This relationship has been proposed to be due in part to the involvement of HDL in reverse cholesterol transport, recent studies have shown that HDL can prevent the oxidation of low-density lipoprotein (LDL) [11]
This prevention of LDL oxidation by HDL contributes to a decrease in the formation of lipid peroxides, foam cell formation and cytotoxicity otherwise caused by oxidized lowdensity lipoprotein (oLDL) [12,13,14]
Summary
An inverse relationship between the level of high-density lipoprotein (HDL) and coronary heart disease (CHD) has been reported. In the present study we have investigated a: the effect of various equine estrogens on HDL oxidation, b: the inhibition of LDL oxidation by HDL and c: the effect of these estrogens on LDL oxidation in the presence of HDL Modified lipoproteins, such as oxidized lowdensity lipoprotein (oLDL) have been implicated in the pathogenesis of atherosclerosis and neurodegenerative diseases such as Alzheimer's disease (AD) [1,2,3,4,5]. Epidemiological data has suggested a strong inverse correlation between plasma HDL concentrations and the incidence of coronary and cerebral atherosclerosis [9,10] This relationship has been proposed to be due in part to the involvement of HDL in reverse cholesterol transport, recent studies have shown that HDL can prevent the oxidation of LDL [11]. OHDL is neurotoxic and has been postulated to play a role in the genesis of coronary artery spasm that contributes to the process of CHD [8,18]
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