Pablo Corral: The ANGPTL Axis in Dyslipidemia and Cardiovascular Risk
Pablo Corral, Pharmacology Professor at FASTA University, Past President of Argentine Lipid Society, shared a post on LinkedIn about a recent article by Isabela C. Bitencourt et al., published in Current Atherosclerosis Reports, adding:
“The Angiopoietin-like Protein (ANGPTL) Axis in Dyslipidemia: Mechanisms, Cardiovascular Risk, and Emerging Therapies
The ANGPTL axis is rapidly becoming one of the most exciting frontiers in lipid therapeutics.
- ANGPTL3 inhibition lowers TG, remnants, LDL-C and apoB — importantly, through mechanisms largely independent of the LDL receptor.
- HoFH is already proof of concept: evinacumab reduced LDL-C by approximately 49%, irrespective of LDLR genotype.
- RNA therapeutics such as zodasiran and solbinsiran are expanding the field, providing sustained ANGPTL3 suppression and broad reductions in atherogenic lipoproteins.
- ANGPTL3/8 and ANGPTL4 are emerging as additional targets, particularly for TG- and remnant-rich dyslipidemia.
- And perhaps the most disruptive concept: one-time in vivo CRISPR-Cas9 editing of ANGPTL3, with early human data showing up to 80% ANGPTL3 suppression and sustained reductions in TG and LDL-C.
The key unanswered question: will these impressive lipid changes translate into fewer cardiovascular events?
The future of lipid lowering may not simply be about targeting another lipid, but about rewiring the pathways that control atherogenic lipoprotein metabolism.”
Title: The Angiopoietin-like Protein (ANGPTL) Axis in Dyslipidemia: Mechanisms, Cardiovascular Risk, and Emerging Therapies
Authors: Isabela C. Bitencourt, André Zimerman, Nicholas A. Marston
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