Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VLDL-2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux

Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

“…Thus, alterations in the constellation of HDL particles elicited by simvastatin treatment do not result in an improvement of RCT in type 1 diabetes mellitus, as far the potential of plasma to stimulate cellderived cholesterol removal is concerned. Comparison of the only data available so far, demonstrates that cholesterol efflux from Fu5AH cells to plasma from type IIB hyperlipidaemic subjects is increased after atorvastatin treatment in association with a pronounced rise in HDL cholesterol and plasma apo A-I [51]. It is unknown whether this difference is due to the patient category studied, the magnitude of the rise in HDL cholesterol and plasma apo A-I after statin treatment or to other factors.…”

“…LDL-cholesterol lowering, in response to the HMG Co-A reductase inhibitor, atorvastatin, is accompanied by a decrease in plasma CETP activity and in cholesteryl ester transfer in hypertriglyceridaemic [49] and in combined hyperlipidaemic subjects [50,51]. This effect on plasma cholesteryl ester transfer is also seen in normolipidaemic subjects treated with simvastatin [23].…”

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…161 Equally, a 6-week long treatment with atorvastatin at 10 mg or 40 mg dose-dependently elevated cellular free cholesterol efflux towards plasma by 15% and 35%, respectively, in subjects with mixed dyslipidemia. 162 This improved cholesterol efflux capacity may be the result of the 24% increase in apoA-I levels observed following atorvastatin therapy. 162 Alternative reasons may be the marked reductions in the CETP-mediated transfer of cholesteryl esters from HDL to apoB-containing lipoproteins, 162 which at least in animal models has been suggested to be atheroprotective.…”

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

“…This result was not confirmed in a more recent paper by the same group (Franceschini et al 2013), likely because of the different HDL particle profile in the two investigated populations of patients. In the first study (Guerin et al 2002), patients displayed a greater content of large HDL particles, whereas in patients with dyslipidemia of the last study (Franceschini et al 2013), the small, ABCA1-interacting HDL was the predominant fraction, and no further increase in this HDL population was observed after fenofibrate therapy, consistent with the lack of changes in ABCA1-mediated CEC. Whether fenofibrate therapy modulate the ability of plasma or HDL to facilitate cholesterol efflux from macrophages has been investigated also in a subset of the FIELD study showing that cholesterol efflux values from macrophage foam cells to HDL and plasma in the fenofibrate group (200 mg/day for 5 years) were comparable to those of the placebo group .…”

“…Khera et al measured HDL CEC in patients treated with 10 and 80 mg atorvastatin or 40 mg pravastatin for 16 weeks and reported no effects of statin therapy on HDL CEC from macrophages expressing all the known cholesterol efflux pathways (ABCA1, ABCG1, SR-BI, and passive diffusion) (Khera et al 2011). As opposed to these results, Guerin et al have shown that atorvastatin therapy for 12 weeks (10 and 40 mg daily) could increase SR-BI-dependent CEC of plasma from patients with type IIB hyperlipidemia, in a dose-dependent manner (Guerin et al 2002). The effect of simvastatin on HDL's ability to promote cholesterol efflux was assessed in a randomized, double-blind, parallel group trial carried out in dyslipidemic patients with low HDL-C levels receiving either fenofibrate (160 mg/day) or simvastatin (40 mg/day) for 8 weeks (Franceschini et al 2007).…”