Related Experiment Video

Updated: Jun 26, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

8.1K

PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease

Wei-Wei Li1, Ze-Ming Guo2, Bing-Cai Wang1

  • 1Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Clinical Hemorheology and Microcirculation
|May 10, 2024
PubMed

Insights

Silencing PCSK9 protein in vascular cells reduces injury and inflammation caused by oxidized LDL. This finding reveals PCSK9

Area of Science:

  • Cardiovascular Biology
  • Cellular and Molecular Medicine
  • Inflammation Research

Background:

  • Atherosclerosis (AS) is a chronic inflammatory arterial disease linked to endothelial dysfunction.
  • Protein convertase subtilin/kexin9 type (PCSK9) is implicated in AS pathogenesis, but its precise mechanism remains elusive.

Purpose of the Study:

  • To investigate the role of PCSK9 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury and autophagy.
  • To elucidate the molecular mechanisms underlying PCSK9's involvement in atherosclerosis.

Main Methods:

  • Established a human umbilical vein endothelial cell (HUVEC) model of coronary atherosclerosis using ox-LDL.
  • Utilized small interfering RNA (siRNA) to silence PCSK9 expression and assessed its effects on HUVEC function and signaling pathways.

Main Results:

  • Ox-LDL induced HUVEC injury, autophagy, and increased PCSK9 expression.
  • PCSK9 silencing ameliorated ox-LDL-induced endothelial dysfunction, inflammation, and apoptosis, while promoting proliferation.
  • PCSK9 silencing modulated autophagy markers (LC3B, p62) and inhibited the PI3K/AKT/mTOR pathway.

Conclusions:

  • PCSK9 silencing mitigates ox-LDL-induced endothelial cell injury and inflammation by inhibiting the PI3K/AKT/mTOR pathway and modulating autophagy.
  • Targeting PCSK9 presents a potential therapeutic strategy for atherosclerosis.
Abstract

Keywords:
PCSK9PI3Katherosclerotic coronaryautophagyendothelial cell

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