Small lipid-binding proteins in regulating endothelial and vascular functions: focusing on adipocyte fatty acid binding protein and lipocalin-2

Br J Pharmacol. 2012 Feb;165(3):603-21. doi: 10.1111/j.1476-5381.2011.01528.x.

Abstract

Dysregulated production of adipokines from adipose tissue plays a critical role in the development of obesity-associated cardiovascular abnormalities. A group of adipokines, including adipocyte fatty acid binding protein (A-FABP) and lipocalin-2, possess specific lipid-binding activity and are up-regulated in obese human subjects and animal models. They act as lipid chaperones to promote lipotoxicity in endothelial cells and cause endothelial dysfunction under obese conditions. However, different small lipid-binding proteins modulate the development of vascular complications in distinctive manners, which are partly attributed to their specialized structural features and functionalities. By focusing on A-FABP and lipocalin-2, this review summarizes recent advances demonstrating the causative roles of these newly identified adipose tissue-derived lipid chaperones in obesity-related endothelial dysfunction and cardiovascular complications. The specific lipid-signalling mechanisms mediated by these two proteins are highlighted to support their specialized functions. In summary, A-FABP and lipocalin-2 represent potential therapeutic targets to design drugs for preventing vascular diseases associated with obesity.

Linked articles: This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute-Phase Proteins / physiology*
  • Animals
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Fatty Acid-Binding Proteins / physiology*
  • Humans
  • Lipocalin-2
  • Lipocalins / physiology*
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Proto-Oncogene Proteins / physiology*

Substances

  • Acute-Phase Proteins
  • Fatty Acid-Binding Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins