Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP

1Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

Abstract

Background: Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. Objective: We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)–containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. Methods: Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days. Results: Reduction in low-density lipoprotein (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42 days (–38%, –32%, and –35%, respectively); rapid reduction equally occurred in remnant cholesterol, ApoCII, CIII, and E levels (day 6; –35%, –50%, –23%, and –26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated at baseline and were markedly reduced on treatment (–29% vs total LDL mass). Cholesteryl ester (CE) transfer protein activity and mass decreased progressively (–18% and –16%, respectively); concomitantly, TG depletion (up to –49%) and CE enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was preferentially depleted from LpAI:AII–rich particles on treatment. Conclusion: Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer protein–mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic ApoB-containing lipoproteins. Normalization of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure, and function.

Cite

CITATION STYLE

APA

Chapman, M. J., Orsoni, A., Robillard, P., Therond, P., & Giral, P. (2018). Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP. Journal of Clinical Lipidology, 12(3), 784-800.e4. https://doi.org/10.1016/j.jacl.2018.02.001

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free