Related Experiment Video

Updated: Mar 21, 2026

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

4.4K

Cross-Talk Between PCSK9 and Damaged mtDNA in Vascular Smooth Muscle Cells: Role in Apoptosis

Zufeng Ding1,2, Shijie Liu1, Xianwei Wang1

  • 11 Central Arkansas Veterans Healthcare System, The University of Arkansas for Medical Sciences , Little Rock, Arkansas.

Antioxidants & Redox Signaling
|May 21, 2016
PubMed
Abstract

Insights

Vascular smooth muscle cell (SMC)-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) induces mitochondrial DNA (mtDNA) damage. This damage, in turn, stimulates further PCSK9 release, creating a cycle that promotes cellular injury and atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Medicine
  • Molecular Cardiology

Background:

  • Vascular smooth muscle cells (SMCs) play a critical role in vascular health.
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily known for its role in cholesterol metabolism.
  • Mitochondrial DNA (mtDNA) damage is implicated in various cellular pathologies.

Purpose of the Study:

  • To investigate the potential interaction between SMC-derived PCSK9 and mtDNA damage.
  • To elucidate the mechanisms underlying this interplay and its functional consequences.

Main Methods:

  • In vitro studies using cultured SMCs treated with lipopolysaccharide (LPS), PCSK9 siRNA, and various mitochondrial toxins.
  • Assessment of mtDNA damage, PCSK9 release, and reactive oxygen species (ROS) production.
  • In vivo studies using wild-type and PCSK9-null mice administered LPS.
  • Analysis of signaling pathways including p38 MAPK and mammalian target of rapamycin (mTOR).

Main Results:

  • Lipopolysaccharide (LPS) stimulated both PCSK9 release and mtDNA damage in SMCs.
  • PCSK9 inhibition reduced mtDNA damage, while enhancement increased it.
  • Mitochondria-derived ROS (mtROS) were involved in the interplay between PCSK9 and mtDNA damage.
  • Bidirectional interplay was observed: mtDNA damage induced PCSK9 expression, and vice versa.
  • SMC apoptosis was increased by recombinant PCSK9 and decreased by PCSK9 siRNA.
  • LPS induced simultaneous PCSK9 release and mtDNA damage in mice, with reduced damage in PCSK9-null mice.

Conclusions:

  • Vascular SMC-derived PCSK9 directly induces mtDNA damage.
  • Damaged mtDNA fragments stimulate further PCSK9 release, partly mediated by mtROS.
  • A positive feedback loop exists between PCSK9 and mtDNA damage in a proinflammatory setting.
  • This interaction contributes to cellular injury and apoptosis, hallmarks of atherosclerosis.
Keywords:
PCSK9apoptosismtDNA damagesmooth muscle cells

More Related Videos

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

8.9K
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK908:14

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

Published on: August 28, 2018

8.7K

Related Concept Videos

Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
1.9K
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
75
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
932
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.7K