Key result
Statin therapy was associated with 15% lower plasma ANGPTL3 concentrations in familial hypercholesterolemia patients compared to statin-naive patients (145 vs 167 ng/ml; p=0.012).
Why the study?
It was unknown whether statins prescribed to hypercholesterolemic patients in clinical practice affect plasma ANGPTL3 concentrations.
Does statin therapy reduce plasma ANGPTL3 concentrations in hypercholesterolemic patients?
Observational (n=168)
Does statin therapy reduce plasma ANGPTL3 concentrations in hypercholesterolemic patients?
Statin therapy reduces plasma ANGPTL3 concentrations in hypercholesterolemic patients, likely through decreased oxysterol-mediated LXR activation.
Answers are grounded in this paper and cite their sources.
Statin-associated ANGPTL3 reductions in FH warrant prospective validation; leaves open effects on outcomes or need for targeted trials.
BACKGROUND AND AIMS: Statins suppress hepatic mRNA expression of ANGPTL3 encoding angiopoietin-like 3 in healthy subjects, but it is unknown if plasma ANGPTL3 concentrations are affected by statins prescribed to hypercholesterolemic patients in clinical practice. We therefore investigated the effect of statin treatment on plasma ANGPTL3 concentrations in hypercholesterolemic patients. In addition, we explored the underlying mechanism by which statins regulate ANGPTL3 in vitro. METHODS: Plasma ANGPTL3 concentrations were measured in 93 genetically confirmed familial hypercholesterolemia (FH) patients who were using statin therapy and 61 statin naïve FH patients. Moreover, concentrations were measured in 14 hypercholesterolemic patients who discontinued their statin treatment for 4 weeks. In vitro studies were performed with Huh7 human hepatoma cells. RESULTS: Plasma ANGPTL3 concentrations were 15% lower in statin treated FH patients compared to statin naïve FH patients (145 (120-193) vs. 167 (135-220) ng/ml, p = 0.012). Statin discontinuation resulted in a 21% (p<0.001) increase of plasma ANGPTL3 concentrations. Simvastatin reduced ANGPTL3 mRNA expression and ANGPTL3 secretion of Huh7 cells. Liver X receptor (LXR) activation with T0901317 increased ANGPTL3 mRNA expression and ANGPTL3 secretion by 6- and 3-fold, respectively. Adding simvastatin did not mitigate this effect but adding the LXR antagonist GSK2230 to simvastatin-incubated Huh7 cells diminished simvastatin-induced reductions in ANGPTL3 mRNA expression and ANGPTL3 secretion. Simvastatin reduced intracellular oxysterol concentrations. Oxysterols are endogenous LXR ligands, implying that simvastatin suppresses ANGPTL3 secretion via reduced oxysterol-mediated LXR activation. CONCLUSIONS: Statins lower plasma ANGPTL3 concentrations in hypercholesterolemic patients, likely due to decreased oxysterol-mediated LXR activation.
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Reeskamp et al. (2020) conducted an observational in Familial hypercholesterolemia (n=168). Statin therapy vs. Statin naïve was evaluated on Plasma ANGPTL3 concentrations (15% lower, p=0.012). Statin therapy was associated with 15% lower plasma ANGPTL3 concentrations in familial hypercholesterolemia patients compared to statin-naive patients (145 vs 167 ng/ml; p=0.012).
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