LDL and apoB
Baseline CETP level predicts how much pitavastatin lowers LDL-C, via LXR-dependent suppression of CETP transcription (Lipids Health Dis 2016)
Original title: Serum CETP status is independently associated with reduction rates in LDL-C in pitavastatin-treated diabetic patients and possible involvement of LXR in its association
In fifty-three patients with type 2 diabetes and hypercholesterolemia treated with 2 mg pitavastatin for 3 months, LDL-C, small dense LDL-C, and CETP levels fell by 39%, 42%, and 23% respectively. Although CETP and LDL-C were not significantly associated at baseline, baseline CETP level and its percentage change were independent positive determinants of the LDL-C and small dense LDL-C reductions achieved. In HepG2 cells, the LXR agonist T0901317 increased CETP mRNA by approximately 220%, an effect largely abolished by LXR silencing, while pitavastatin alone decreased basal CETP mRNA by 21%, an effect completely reversed by T0901317, indicating pitavastatin lowers CETP expression partly by reducing hepatic LXR activity, and that baseline CETP status can predict a patient's statin response.
Original abstract
Background: Statins decrease cholesteryl ester transfer protein (CETP) levels, which have been positively associated with hepatic lipid content as well as serum low density lipoproteins-cholesterol (LDL-C) levels. However, the relationship between the CETP status and statin-induced reductions in LDL-C levels has not yet been elucidated in detail. We herein examined the influence of the CETP status on the lipid-reducing effects of pitavastatin in hypercholesterolemic patients with type 2 diabetes mellitus as well as the molecular mechanism underlying pitavastatin-induced modifications in CETP levels.
Methods: Fifty-three patients were treated with 2 mg of pitavastatin for 3 months. Serum levels of LDL-C, small dense (sd) LDL-C, and CETP were measured before and after the pitavastatin treatment. The effects of pitavastatin, T0901317, a specific agonist for liver X receptor (LXR) that reflects hepatic cholesterol contents, and LXR silencing on CETP mRNA expression in HepG2 cells were also examined by a real-time PCR assay.
Results: The pitavastatin treatment decreased LDL-C, sdLDL-C, and CETP levels by 39, 42, and 23%, respectively. Despite the absence of a significant association between CETP and LDL-C levels at baseline, baseline CETP levels and its percentage change were an independent positive determinant for the changes observed in LDL-C and sdLDL-C levels. The LXR activation with T0901317 (0.5 μM), an in vitro condition analogous to hepatic cholesterol accumulation, increased CETP mRNA levels in HepG2 cells by approximately 220%, while LXR silencing markedly diminished the increased expression of CETP. Pitavastatin (5 μM) decreased basal CETP mRNA levels by 21%, and this was completely reversed by T0901317.
Conclusion: Baseline CETP levels may predict the lipid-reducing effects of pitavastatin. Pitavastatin-induced CETP reductions may be partially attributed to decreased LXR activity, predictable by the ensuing decline in hepatic cholesterol synthesis.
Trial Registration: UMIN Clinical Trials Registry ID UMIN000019020.
diabetesLDL and apoBliverstatins
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.