New and Emerging Therapeutic Targets for ApoB-Containing Particles Lowering

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Pharmacology

Background:

• Apolipoprotein B (apoB) is the structural protein of all atherogenic lipoproteins, including VLDL, IDL, LDL, and Lp(a).
• Plasma apoB concentration directly reflects the number of circulating atherogenic particles.
• Elevated apoB is linked to atherosclerotic cardiovascular disease (ASCVD) and triglyceride-mediated acute pancreatitis.

Purpose of the Study:

• To highlight apoB as a more accurate determinant of ASCVD risk than LDL cholesterol alone.
• To review current and emerging therapies that modulate apoB-containing lipoproteins.
• To advocate for an apoB-centric framework for risk assessment and management.

Main Methods:

• Review of genetic, epidemiological, and clinical trial evidence supporting apoB's role in ASCVD.
• Analysis of established and novel therapeutic strategies targeting apoB metabolism and clearance.
• Discussion of the biological integration of apoB modulation for multiple disease risks.

Main Results:

• Evidence consistently shows apoB is a superior causal determinant of ASCVD risk per particle compared to LDL cholesterol.
• Most cardiovascular therapies (statins, PCSK9 inhibitors) primarily reduce apoB by enhancing LDL receptor-mediated clearance.
• Emerging therapies and gene-targeted approaches offer expanded opportunities for durable apoB modulation.

Conclusions:

• Shifting to an apoB-centric approach provides a biologically integrated strategy for reducing ASCVD and pancreatitis risk.
• Targeting apoB offers a unified therapeutic goal for managing dyslipidemias and their associated complications.
• Novel therapeutic strategies promise more effective and durable modulation of atherogenic lipoproteins.