Physicians' Academy for Cardiovascular Education

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-III

Literature - Pechlaner R, Tsimikas S, Yin X, et al. - J Am Coll Cardiol 2017;69:789-800


CVD risk is mainly associated with specific lipids that belong to certain lipoprotein classes, such as LDL-C and VLDL, although individual molecular lipid species within the same lipid class have different associations with CVD [1]. Lipoprotein functions and metabolism are predominantly dependent on their apolipoprotein content, but no comprehensive analysis of plasma apolipoproteins and lipids has been performed in the same cohort to assess their comparative association with future CVD.

In this study, apolipoproteins were directly measured by mass spectrometry, and their associations with incident CVD were compared. The measurements were based on multiple-reaction monitoring mass spectrometry (MRM-MS), and the associations of apolipoproteins with incident CVD were investigated in 688 individuals included in the prospective population-based Bruneck Study [1]. Moreover, the effect of the inhibition of hepatic apoC-III synthesis with volanesorsen was tested in plasma samples [2-4].

Main results


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.


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