Differential impact of oleate, palmitate, and adipokines on expression of NF-κB target genes in human vascular smooth muscle cells

Mol Cell Endocrinol. 2012 Oct 15;362(1-2):194-201. doi: 10.1016/j.mce.2012.06.010. Epub 2012 Jun 28.

Abstract

It is widely accepted that obesity is a major risk factor for the development of atherosclerosis. In this context, adipose tissue produces a variety of adipokines and releases free fatty acids, contributing to a chronic-low grade inflammation state implicated in vascular complications. In this study, we investigated the role of adipokines, oleic acid (OA), palmitic acid (PA), and the combinations on activation of NF-κB target genes in human vascular smooth muscle cells (SMC) to assess the hypothesis of synergistic interactions between these molecules. Adipocyte-conditioned medium (CM), generated from human adipocytes, in combination with low concentrations of OA, but not PA, induces SMC proliferation and activation of the transcription factor NF-κB in a synergistic way. Combined treatment of CM and OA further regulates a set of downstream NF-κB target genes including angiopoietin-1, activin A, and MMP-1, all critically involved in SMC dysfunction. This suggests that the lipotoxic potential of fatty acids is substantially enhanced by the presence of adipocyte-derived factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / genetics
  • Activins / metabolism
  • Adipocytes / metabolism
  • Adipokines / pharmacology
  • Adipokines / physiology*
  • Angiopoietins / genetics
  • Angiopoietins / metabolism
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Culture Media, Conditioned
  • Female
  • Gene Expression
  • Gene Expression Regulation
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Middle Aged
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / physiology
  • NF-kappa B / metabolism*
  • Obesity / metabolism
  • Obesity / pathology
  • Oleic Acid / pharmacology
  • Oleic Acid / physiology*
  • Palmitic Acid / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology
  • Vasculitis / metabolism
  • Vasculitis / pathology

Substances

  • Adipokines
  • Angiopoietins
  • Apoptosis Regulatory Proteins
  • CCL5 protein, human
  • CIDEA protein, human
  • Chemokine CCL5
  • Culture Media, Conditioned
  • IL6 protein, human
  • Interleukin-6
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • activin A
  • Activins
  • Oleic Acid
  • Palmitic Acid
  • MMP1 protein, human
  • Matrix Metalloproteinase 1