AI Article Synopsis

  • * After treatment with PCSK9 inhibitors, plasma from FH patients showed altered cholesterol distribution, with less cholesterol in LDL and more in HDL.
  • * PCSK9 inhibitors enhanced the movement of cholesterol to feces in specific mouse models and support the reverse cholesterol transport pathway in patients with heterozygous FH.

Article Abstract

We investigated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies to restore macrophage cholesterol efflux in subjects with heterozygous familial hypercholesterolemia (FH) and to enhance the macrophage-specific reverse cholesterol transport pathway in mice. Analyses of macrophage-derived cholesterol distribution of plasma from FH patients revealed that low-density lipoprotein (LDL) particles contained less, and high-density lipoprotein particles contained more radiolabeled cholesterol after treatment with either PCSK9 inhibitor. PCSK9 antibodies facilitated the transfer of macrophage-derived cholesterol and LDL-derived cholesterol to feces exclusively in heterozygous LDL receptor-deficient mice expressing human APOB100. PCSK9 inhibitors act as positive regulators of the macrophage-specific reverse cholesterol transport pathway in individuals with heterozygous FH.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551875PMC
http://dx.doi.org/10.1016/j.jacbts.2024.06.008DOI Listing

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