Pitavastatin Decreases Plasma Pre.BETA.1-HDL Concentration and Might Promote its Disappearance Rate in Hypercholesterolemic Patients

Abstract

Aim: Pre 1-HDL is involved in the initial step of cholesterol efflux from peripheral cells and plays an important role in reverse cholesterol transport. We studied the effect of pitavastatin on the HDL subfraction profile, pre 1-HDL concentration and its disappearance rate. Methods: Twenty-nine hypercholesterolemic patients were treated with pitavastatin at 2 mg/day for 4 weeks, and plasma levels of total cholesterol (TC), triglyceride, HDL-cholesterol (C), HDL2-C, HDL3-C, pre 1-HDL, LCAT activity, and CETP mass were assayed. The pre 1-HDL disappearance rate was determined as the difference in pre 1-HDL concentration before and after incubation at 37 for 90 min divided by the pre-incubation pre 1-HDL concentration. Results: Pitavastatin led to significant decreases in TC by 26.9% and LDL-C by 39.8%. HDL-C and HDL2-C increased significantly by 6.0% and 9.0%, respectively, but there was no significant change in HDL3-C. Pre 1-HDL concentration significantly decreased ( 8.7%; p 0.05); however, its disappearance rate significantly increased (13.0%; p 0.05). There were significant decreases in both LCAT activity and CETP mass. Conclusion: Although pitavastatin decreased plasma pre 1-HDL concentration, it increased the pre 1-HDL disappearance rate. These data suggest that pitavastatin might promote the early step of reverse cholesterol transport. J Atheroscler

Evidence for the presence of lipid-free monomolecular apolipoprotein A-1 in plasma

“…It is known that when plasma is incubated at 37°C, the concentration of plasma pre ␤ 1-HDL decreases and this decrease is blocked by the presence of DTNB ( 10,21,45,47 ). Although the mechanism has not yet been clarifi ed, the phenomenon seems to be a LCAT-dependent effect because it has been reported that the same effect is shown when anti-LCAT antibody is used instead of DTNB ( 47 ), and that plasma LCAT activity is positively correlated with the decreased level of plasma pre ␤ 1-HDL in the experiment ( 25 ). In the present study, lipid-free apoA-1 added to pre ␤ 1-HDL-depleted plasma showed the same variation in concentration as plasma pre ␤ 1-HDL in a LCAT-dependent manner ( Fig.…”

“…We previously obtained a monoclonal antibody (MAb) 55201 (MAb55201) that specifically recognizes apoA-1 in pre ␤ 1-HDL and developed an ELISA for easily measuring plasma pre ␤ 1-HDL concentrations using the MAb ( 21 ). Recently a variety of research results on pre ␤ 1-HDL using the ELISA were reported, in particular the relationships between plasma pre ␤ 1-HDL concentrations and coronary artery disease and medications have been noted (22)(23)(24)(25)(26).…”

Rosuvastatin Activates ATP-Binding Cassette Transporter A1–Dependent Efflux Ex Vivo and Promotes Reverse Cholesterol Transport in Macrophage Cells in Mice Fed a High-Fat Diet

“…Several clinical trials have reported that aggressive lipid-lowering therapy not only suppresses the progression of atherosclerosis, but also contributes to its regression. [9][10][11] Although the administration of rosuvastatin and atorvastatin resulted in a significant regression of coronary atherosclerosis 12 and significantly increased HDL-C levels, [12][13][14][15][16] the effects of statins on the 3 stages of RCT in vivo have not yet been reported. We hypothesized that these strong statins might promote the expression of several factors involved in RCT independent of lowering LDL-C, and there might be differences in the effects of rosuvastatin and atorvastatin on RCT.…”

Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl ester transfer protein in type 2 diabetes mellitus

“…This may simply reflect the effects of lipid-lowering drugs, because statins also decrease CETP mass in hypercholesterolemic patients [12]. Alternatively, ezetimibe may regulate the CETP gene at transcriptional levels.…”

“…We recently reported that pitavastatin decreases CETP mass and LCAT activity in hypercholesterolemic patients [12]. Furthermore, genome-wide association studies involving >100,000 individuals of European ancestry identified LCAT and CETP as significantly associated loci with plasma HDL-C [13].…”