Endothelial Dysfunction in Obesity

Adv Exp Med Biol. 2017;960:345-379. doi: 10.1007/978-3-319-48382-5_15.

Abstract

Chronic inflammatory state in obesity causes dysregulation of the endocrine and paracrine actions of adipocyte-derived factors, which disrupt vascular homeostasis and contribute to endothelial vasodilator dysfunction and subsequent hypertension. While normal healthy perivascular adipose tissue (PVAT) ensures the dilation of blood vessels, obesity-associated PVAT leads to a change in profile of the released adipo-cytokines, resulting in a decreased vasorelaxing effect. Adipose tissue inflammation, nitric oxide (NO)-bioavailability, insulin resistance and oxidized low-density lipoprotein (oxLDL) are main participating factors in endothelial dysfunction of obesity. In this chapter, disruption of inter-endothelial junctions between endothelial cells, significant increase in the production of reactive oxygen species (ROS), inflammation mediators, which are originated from inflamed endothelial cells, the balance between NO synthesis and ROS , insulin signaling and NO production, and decrease in L-arginine/endogenous asymmetric dimethyl-L-arginine (ADMA) ratio are discussed in connection with endothelial dysfunction in obesity.

Keywords: Asymmetric dimethyl-L-arginine (ADMA); Cyclic guanosine monophosphate (cGMP); Endothelial nitric oxide synthase (eNOS); Endothelial nitric oxide synthase (eNOS) uncoupling; Endothelin-1 (ET-1); Endothelium; Inducible nitric oxide synthase (iNOS); Intercellular adhesion molecule-1 (ICAM-1); Low-density lipoproteins (LDL); Nitric oxide (NO); Nuclear factor kappa-B (NF-kappaB); Obesity; Oxidized low-density lipoprotein (OxLDL); Peroxynitrite; Plasminogen-activator inhibitor-1 (PAI-1); Protein kinase C (PKC); Pyrin domain-containing 3 (NLRP3) inflammasome; Reactive oxygen species (ROS); Saturated fatty acids; Super oxide dismutase (SOD); Tumor necrosis factor-alpha (TNF-alpha); Vascular cell adhesion molecule-1 (VCAM-1); Vascular endothelial growth factor (VEGF); Vasodilatory-stimulated phosphoprotein (VASP).

Publication types

  • Review

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Cytokines / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Obesity / metabolism
  • Obesity / pathology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology

Substances

  • Cytokines
  • Reactive Oxygen Species