Resveratrol and lipoproteins

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Target disruption of the apolipoprotein E (apoE) or low-density lipoprotein receptor  (LDLR) genes, as well as overexpression of the human apolipoprotein B (apoB) gene in mice, result in marked increases in VLDL (very low-density lipoprotein) and /or LDL levels and subsequently contribute to atherosclerosis promotion [7]. In hypercholesterolemic mice (apoE-/-/LDLR-/-), resveratrol decreases the plasma lipid concentrations (total cholesterol and triacylglycerols) and reduces platelet aggregates [8]. The plasmatic concentration of lipids can also be reduced by the action of other apolipoproteins such as apoB or apolipoprotein I/II (apo I/II). So, resveratrol is able to reduce apoB content and secretion (which may be responsible for impaired LDL and VLDL synthesis) as well as the intracellular content and the rate of secretion of cholesteryl esters from hepatoblastoma cells [9, 10]. The rate of secretion of triglycerides (TGs) is also reduced by resveratrol, but the intracellular TGs content is unaffected. Taken together, these changes would tend to decrease the level of VLDLs which are riche in TGs and possess potential atherogenic properties (direct supply of cholesterol to fibroblasts; alterations of endothelial functions; transformation of monocytes-macrophages in foam cells). These events are found also in vivo in rats where resveratrol treatment dcreases serum TGs, VLDL+LDL-cholesterol levels [11]. By its estrogenic similar structure, resveratrol could act on apoII. Indeed, hepatic expression of apoII is in part modulated by estrogen-mediated stabilization of its mRNA which is due to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF). E-RmRNASF protect the RNA from target endonucleolytic degradation and its hepatic expression is modulated by estrogenic xenobiotics. Resveratrol seems to act as phyto-estrogens and it appears that resveratrol acts as an agonistic compound stimulating the E-RmRNASF expression [12]. These results suggest that resveratrol would have the capacity to modulate and block certain aspects of hepatic lipoprotein metabolism which predispose to atherosclerosis and the hypocholesterolemic action of resveratrol could be attributed to an increased excretion of neutral sterols and bile acids into feces.