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 journalArticle

13 Citations (Scopus)

Abstract

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
JournalHypertension
Volume60
Issue number4
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Caveolin 1
Apolipoproteins
Apolipoproteins E
Nitric Oxide Synthase
Macrophages
Endothelial Cells
Sterols
Confocal Microscopy
Vasodilation
Acetylcholine
Adipose Tissue
Arteries

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase. / Yue, Lili; Bian, Jing Tan; Grizelj, Ivana; Cavka, Ana; Phillips, Shane A.; Makino, Ayako; Mazzone, Theodore.

In: Hypertension, Vol. 60, No. 4, 10.2012, p. 1040-1046.

Research output: Contribution to journalArticle

Yue, Lili ; Bian, Jing Tan ; Grizelj, Ivana ; Cavka, Ana ; Phillips, Shane A. ; Makino, Ayako ; Mazzone, Theodore. / Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase. In: Hypertension. 2012 ; Vol. 60, No. 4. pp. 1040-1046.
@article{60098dbffbd946d6bdf0e1e40c1342e8,
title = "Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase",
abstract = "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.",
keywords = "apolipoprotein E, caveolin 1, endothelium, macrophages, NO, NO synthase",
author = "Lili Yue and Bian, {Jing Tan} and Ivana Grizelj and Ana Cavka and Phillips, {Shane A.} and Ayako Makino and Theodore Mazzone",
year = "2012",
month = "10",
doi = "10.1161/HYPERTENSIONAHA.112.196667",
language = "English (US)",
volume = "60",
pages = "1040--1046",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase

AU - Yue, Lili

AU - Bian, Jing Tan

AU - Grizelj, Ivana

AU - Cavka, Ana

AU - Phillips, Shane A.

AU - Makino, Ayako

AU - Mazzone, Theodore

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - apolipoprotein E

KW - caveolin 1

KW - endothelium

KW - macrophages

KW - NO

KW - NO synthase

UR - http://www.scopus.com/inward/record.url?scp=84866537810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866537810&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.112.196667

DO - 10.1161/HYPERTENSIONAHA.112.196667

M3 - Article

VL - 60

SP - 1040

EP - 1046

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 4

ER -