The most negatively charged low-density lipoprotein L5 induces stress pathways in vascular endothelial cells

J Vasc Res. 2012;49(4):329-41. doi: 10.1159/000337463. Epub 2012 May 23.

Abstract

Background/aims: L5, the most negatively charged species of low-density lipoprotein (LDL), has been implicated in atherogenesis by inducing apoptosis of endothelial cells (ECs) and inhibiting the differentiation of endothelial progenitor cells. In this study, we compared the effects of LDL charge on cellular stress pathways leading to atherogenesis.

Methods: We isolated L5 and L1 (the least negatively charged LDL) from the plasma of patients with familial hypercholesterolemia and used JC-1 staining to examine the effects of L5 and L1 on the mitochondrial membrane potential (DCm) in human umbilical vein ECs (HUVECs). Additionally, we characterized the gene expression profiles of 7 proteins involved in various types of cellular stress.

Results: The DCm was severely compromised in HUVECs treated with L5. Furthermore, compared with L1, L5 induced a decrease in mRNA and protein expression of the endoplasmic reticulum (ER) chaperone proteins ORP150, Grp94, and Grp58, mitochondrial proteins Prdx3 and ATP synthase, and an increase in the expression of the pro-inflammatory protein hnRNP C1/C2.

Conclusions: Our work suggests that L5, but not L1, may promote the destruction of ECs that occurs during atherogenesis by causing mitochondrial dysfunction and modulating the expression of key proteins to promote inflammation, ER dysfunction, oxidative stress, and apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis
  • Child
  • Female
  • HSP70 Heat-Shock Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group C / biosynthesis
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Potential, Mitochondrial / drug effects
  • Peroxiredoxin III / biosynthesis
  • Protein Disulfide-Isomerases / biosynthesis
  • Proteins / metabolism
  • Stress, Physiological / drug effects*

Substances

  • HSP70 Heat-Shock Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • Lipoproteins, LDL
  • Membrane Glycoproteins
  • Proteins
  • endoplasmin
  • low-density lipoprotein L5, human
  • oxygen-regulated proteins
  • PRDX3 protein, human
  • Peroxiredoxin III
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human