Inhibition of hepatic apoC-III synthesis lowers atherogenic VLDL-associated lipoproteins
Very-Low-Density Lipoprotein–Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-IIILiterature - Pechlaner R, Tsimikas S, Yin X, et al. - J Am Coll Cardiol 2017;69:789-800
- Among 13 apolipoproteins quantified by MRM-MS, the most significant associations with incident CVD were detected for apoC-II, apoC-III, and apoE (P < 0.001 each, after adjustment for age, gender, and statin therapy), followed by apoL-I, apoB-100, and apoH (p ≤ 0.01 each).
- Additional adjustment for DM, SBP, and current smoking did not significantly change these associations, but further adjustment for HDL-C and non–HDL-C rendered apoB-100 and apo-H non-significant, and weakened the associations obtained for apoC-III, apoC-II, and apoE.
- The association of TGs with CVD (P < 0.001) lost significance after adjustment for HDL-C and non–HDL-C. Similar results were obtained for the individual endpoints of stroke and MI.
- Correlations among apolipoproteins: ApoC-II, apoC-III, apoE, and TGs formed one set of highly inter-correlated variables along with non–HDL-C and apoB-100.
- ApoC-I, which is known to primarily associate with VLDL, correlated most strongly with the apoB-100 cluster, and more weakly with apoA-I and HDL-C.
- The inhibition of hepatic apoC-III synthesis with volanesorsen reduced significantly the plasma apoC-III levels in all subjects (mean decreases >75%), as well as the plasma levels of apoC-II, apoC-III, triacylglycerols, and diacylglycerols, and increased apoA-I, apoA-II and apo-M (all P<0.05 vs. placebo), whereas the levels of apoB-100 (P=0.73) remained unchanged.
The apolipoproteins apoC-III, apoC-II, and apoE that are found on triglyceride-rich lipoproteins regulate their metabolism. They were found to be stronger predictors of CV events compared with other apolipoproteins, including apoB-100. The inhibition of hepatic apoC-III synthesis with volanesorsen has favourable effects on apolipoprotein and lipid profiles, and might represent a new approach to further reduce of CVD risk.