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PCSK9 and LRP6: potential combination targets to prevent and reduce atherosclerosis

Saskia R Desita1, Arisvia S Hariftyani1, Ayik R Jannah1

  • 1Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

Journal of Basic and Clinical Physiology and Pharmacology
|April 16, 2022
PubMed

Insights

This study explores novel therapeutic targets for coronary artery disease (CAD). It investigates inhibiting PCSK9 and LRP6 to reduce atherosclerosis plaque formation and stabilize existing plaques, potentially preventing sudden cardiac death.

Area of Science:

  • Cardiovascular Science
  • Molecular Biology
  • Genetics

Background:

  • Coronary artery disease (CAD) and atherosclerosis are increasing health concerns.
  • Atherosclerosis involves LDL accumulation, endothelial dysfunction, and plaque formation.
  • PCSK9 and LRP6 are key molecular players in atherosclerosis pathogenesis.

Purpose of the Study:

  • To investigate therapeutic strategies targeting PCSK9 and LRP6 for atherosclerosis.
  • To evaluate the impact of inhibiting PCSK9 on LDL-C levels.
  • To explore LRP6 inhibition's effects on VSMCs, macrophages, and lipids.

Main Methods:

  • Utilizing EMPs mediated miRNA-126 for LRP6 inhibition.
  • Employing third-generation antisense against miR-494-3p (3 GA-494).
  • Administering recombinant Wnt mouse Wnt3a (rmWnt3a).

Main Results:

  • PCSK9 inhibition decreases LDLR degradation and lowers LDL-C.
  • LRP6 inhibition reduces VSMC proliferation.
  • Targeting LRP6 enhances anti-inflammatory macrophages and diminishes bioactive lipids.

Conclusions:

  • Inhibiting PCSK9 and LRP6 offers potential therapeutic benefits for atherosclerosis.
  • These strategies can lead to atherosclerosis plaque stabilization and reduction.
  • Novel approaches may mitigate the rising prevalence of CAD.

Keywords:
LRP6PCSK9atherosclerosiscoronary heart disease

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