Regulation der Expression von Scavenger Receptor BI (SR-BI) und des bidirektionalen Cholesterolflux durch den Cholesterol- und Vitamin-E-Gehalt in HepG2-Zellen und High Density Lipoproteinen

Der Scavenger Receptor BI (SR-BI) vermittelt den selective lipid transfer von Cholesterol und Vitamin E aus HDL in die Leber. Die zelluläre Aufnahme verschiedener Lipide aus HDL über den selben Mechanismus, vermittelt durch den selben Rezeptor wirft die Frage auf, ob diese Aufnahmeprozesse einander beeinflussen. Aktuelle Forschungsergebnisse zeigen, daß die Aufnahme von neutralen Lipiden (Cholesterolester, Triacylglycerol) aus HDL in die Zelle von der Lipidzusammensetzung der Donorpartikel abhängen könnte. Wir untersuchten, ob der Vitamin-E-Gehalt von HDL die Aufnahme und den Efflux von Cholesterol in und aus HepG2-Zellen beeinflußt. Die Inkubation von HepG2-Zellen mit [3H]Cholesterol-markiertem HDL mit ansteigendem Vitamin-E-Gehalt ergab eine steigende Aufnahme von Vitamin E, während sich die Cholesterolaufnahme nicht veränderte. Der erhöhte zelluläre Gehalt an Vitamin E bewirkte eine Reduktion der PKC-Alpha- und SR-BI-Expression in Verbindung mit einem erniedrigten Cholesterolefflux aus HepG2-Zellen zu nativem HDL als Akzeptorpartikel. Die Verarmung der Zellen an Cholesterol führte zu einer erniedrigten PKC-Alpha- und SR-BI-Expression. Hingegen veränderte die Erhöhung des zellulären Cholesterolgehalts von HepG2-Zellen die PKC-Alpha- und SR-BI-Expression nicht, während der Cholesterolefflux aus HepG2-Zellen zu HDL im Vergleich zur Kontrolle gesteigert war. Wir schließen aus diesen Ergebnissen, daß Vitamin E und Cholesterol die SR-BI-Expression modulieren können und daß SR-BI den Efflux und möglicherweise auch den Influx von Cholesterol in HepG2-Zellen vermittelt.The scavenger receptor BI (SR-BI) mediates selective lipid transfer of cholesterol and vitamin E from HDL to the liver. Cellular uptake of different lipids from HDL by the same mechanism, mediated by the same receptor rise the question, whether these uptake processes affect each other. Recent results show that the cellular uptake of neutral lipids (cholesterol ester, triacylglycerol) from HDL may depend on the lipid composition of the donor particles. We investigated whether the vitamin E-content of HDL affects cholesterol uptake and efflux by HepG2 cells. Incubation of HepG2 cells with [3H]cholesterol-labeled HDL, which contained increasing vitamin E-concentrations resulted in an increased uptake of vitamin E, whereas the cholesterol uptake did not change. The increased cellular content of vitamin E caused a decreased PKCalpha and SR-BI-expression combined with a decreased cholesterol-efflux from HepG2 cells to native HDL as acceptor. Depletion of cellular cholesterol decreased PKC-alpha and SR-BI-expression in HepG2 cells. Increase of cellular cholesterol of HepG2 cells, however, did not change PKCalpha and SR-BI-expression, whereas cholesterol-efflux from HepG2 cells to HDL increased. We conclude that vitamin E and cholesterol can modulate the SR-BI-expression and that SR-BI mediates the efflux and possibly also the influx of cholesterol by HepG2 cells

Right ventricular function and vasoactive peptides for early prediction of bronchopulmonary dysplasia

Background To assess the prognostic value of early echocardiographic indices of right ventricular function and vasoactive peptides for prediction of bronchopulmonary dysplasia (BPD) or death in very preterm infants. Methods Prospective study involving 294 very preterm infants (median [IQR] gestational age 28.4 [26.4-30.4] weeks, birth weight 1065 [800-1380] g), of whom 57 developed BPD (oxygen supplementation at 36 weeks postmenstrual age) and 10 died. Tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) were measured on day 7 of life. Results RIMP was significantly increased (median [IQR] 0.3 [0.23-0.38] vs 0.22 [0.15-0.29]), TAPSE decreased (median [IQR] 5.0 [5.0-6.0] vs 6.0 [5.4-7.0] mm), MR-proANP increased (median [IQR] 784 [540-936] vs 353 [247-625] pmol/L), and CT-proET1 increased (median [IQR] 249 [190-345] vs 199 [158-284] pmol/L) in infants who developed BPD or died, as compared to controls. All variables showed significant but weak correlations with each other (r(S) -0.182 to 0.359) and predicted BPD/death with similar accuracy (areas under receiver operator characteristic curves 0.62 to 0.77). Multiple regression revealed only RIMP and birth weight as independent predictors of BPD or death. Conclusions Vasoactive peptide concentrations and echocardiographic assessment employing standardized measures, notably RIMP, on day 7 of life are useful to identify preterm infants at increased risk for BPD or death