title: Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women.
abstract: Functional foods enriched with plant stanols lower atherogenic LDL cholesterol concentrations. This effect is caused at least partly by a decreased intestinal cholesterol absorption. It has been suggested that LDL production is reduced after plant stanol consumption, but it is unknown whether LDL receptor expression is affected and contributes to the LDL-lowering effect of plant stanols. Markers for endogenous cholesterol synthesis (lathosterol) increase, but it is not known how this higher cholesterol synthesis is regulated at the molecular level. In a double-blind placebo controlled trial, we have found that compared with the control group (N=15), daily consumption of 3.8-4.0 g plant stanol esters (N=29) for 8 weeks increased LDL receptor mRNA levels in human mononuclear blood cells by 43% (P=0.003). LDL receptor protein concentrations on the surface of monocytes and T lymphocytes increased by 37% (P=0.003) and 25% (P=0.013), suggesting an increased translation. This increased protein expression appeared to be functional, since changes in serum LDL cholesterol correlated negatively with changes in LDL receptor mRNA levels (r=-0.361; P=0.015) and changes in LDL receptor protein expression in monocytes (r=-0.440; P<0.001) and T lymphocytes (r=-0.307; P=0.018). Based on these results, we suggest that the higher LDL receptor expression contributed to a lowered LDL formation along the apoB cascade. Whole body cholesterol synthesis increased, as indicated by the rise in serum cholesterol-standardized lathosterol concentrations, but the 34% increased HMG-CoA reductase mRNA concentrations did not reach statistical significance. Nor did it correlate significantly with changes in serum cholesterol-standardized lathosterol concentrations. This suggests that HMG-CoA reductase may be only partly regulated at a transcriptional level.
authors.affiliation: Department of Human Biology, Maastricht University, 6200 MD, Maastricht, The Netherlands. J.Plat@HB.UNIMAAS.NL
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
mesh_terms: D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004952:Esters / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010840:Phytosterols / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D004952:Esters; D010840:Phytosterols; D012333:RNA, Messenger; D011973:Receptors, LDL; C001521:lathosterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases