Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase

Lili Yue, Jing Tan Bian, Ivana Grizelj, Ana Cavka, Shane A. Phillips, Ayako Makino, Theodore Mazzone

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Apolipoprotein E (apoE) is widely expressed in mammalian tissues, and one of the important tissue-specific effects is the atheroprotection ascribed to macrophage-derived apoE in the arterial wall. However, underlying mechanisms are not well understood. In this study, using subcellular fractionation, confocal microscopy, and coimmunoprecipitation, we demonstrated that macrophage-derived apoE is internalized by endothelial cells and impacts the subcellular distribution/interaction of caveolin 1 (cav-1) and endothelial NO synthase (eNOS). The addition of apoE disrupts the heteromeric complex formed between cav-1 and eNOS, and increases NO production. Sterol and oxysterol enhance endothelial cav-1/eNOS interaction and suppress NO production, but these effects are reversed by apoE. Silencing endothelial cav-1 attenuates apoE-induced NO production, establishing the importance of the cav-1-eNOS interaction for the increment in endothelial NO produced by apoE. Consistent with these observations, macrophage-derived apoE significantly improves vasodilation to acetylcholine in resistance arteries isolated from adipose tissue of obese humans. We conclude that macrophage-derived apoE enhances endothelial NO production by disrupting the inhibitory interaction of eNOS with cav-1. These results establish a novel mechanism by which apoE modulates endothelial cell function.

Original languageEnglish (US)
Pages (from-to)1040-1046
Number of pages7
Issue number4
StatePublished - Oct 2012
Externally publishedYes


  • NO
  • NO synthase
  • apolipoprotein E
  • caveolin 1
  • endothelium
  • macrophages

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase'. Together they form a unique fingerprint.

Cite this