ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components

Yu Yamazaki, Mitsuru Shinohara, Akari Yamazaki, Yingxue Ren, Yan W. Asmann, Takahisa Kanekiyo, Guojun Bu

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: The ε4 allele of the APOE gene (APOE4) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear. Approach and Results: Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice. CONCLUSIONS: ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.

Original languageEnglish (US)
Pages (from-to)128-144
Number of pages17
JournalArteriosclerosis, thrombosis, and vascular biology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Apolipoprotein E4
Pericytes
Apolipoproteins E
Basement Membrane
Protein Isoforms
Apolipoprotein E3
Brain
Extracellular Matrix Proteins
Amyloid
Endothelial Cells
Alleles
Cell Wall
Blood Proteins
Alzheimer Disease
Pathology
Phenotype
Genes

Keywords

  • Alzheimer disease
  • blood-brain barrier
  • collagen IV
  • extracellular matrix
  • pericytes
  • risk factors
  • tight junction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components. / Yamazaki, Yu; Shinohara, Mitsuru; Yamazaki, Akari; Ren, Yingxue; Asmann, Yan W.; Kanekiyo, Takahisa; Bu, Guojun.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 40, No. 1, 01.01.2020, p. 128-144.

Research output: Contribution to journalArticle

Yamazaki, Yu ; Shinohara, Mitsuru ; Yamazaki, Akari ; Ren, Yingxue ; Asmann, Yan W. ; Kanekiyo, Takahisa ; Bu, Guojun. / ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components. In: Arteriosclerosis, thrombosis, and vascular biology. 2020 ; Vol. 40, No. 1. pp. 128-144.
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