Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Treatment of severe hypercholesterolemia in apolipoprotein e-deficient mice by bone-marrow transplantation

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Boisvert, W. A.
  • Spangenberg, J.
  • Curtiss, Linda

publication date

  • August 1995

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Apo E, a key regulator of cholesterol-rich lipoprotein metabolism, is synthesized by numerous extrahepatic tissues. Although its synthesis in macrophages is documented, the contribution of macrophage-derived apo E to hepatic clearance of serum cholesterol is unknown. To address this issue bone marrow transplantation was performed on hypercholesterolemic apo E-deficient mice with either syngeneic apo E-deficient mouse bone marrow cells (E0-control) or wild-type mouse bone marrow cells expressing apo E (E0-treated). E0-control and E0-treated mice were fed either a regular chow diet or an atherogenic diet (designated E0-control-HF and E0-treated-HF). Serum cholesterol levels dropped dramatically in the E0-treated mice largely due to a reduction in their VLDL cholesterol. No changes were seen in the E0-control mice. After 4 wk serum cholesterol in E0-treated-HF mice was about four-fold lower compared to E0-control-HF animals. Moreover, the extent of atherosclerosis in the E0-treated-HF mice after 14-16 wk was greatly reduced. Wild-type apo E mRNA was detected in the liver, spleen, and brain of the E0-treated mice indicating that apo E gene transfer was successfully achieved through bone marrow transplantation. More importantly, the level of apo E expression was sufficient to reduce the severe hypercholesterolemia of the apo E-deficient mice fed either chow or atherogenic diets.

subject areas

  • Alleles
  • Animals
  • Apolipoproteins E
  • Arteriosclerosis
  • Base Sequence
  • Bone Marrow Transplantation
  • Cholesterol
  • Diet, Atherogenic
  • Gene Transfer Techniques
  • Genetic Therapy
  • Hyperlipoproteinemia Type II
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Organ Specificity
  • Polymerase Chain Reaction
  • RNA, Messenger
scroll to property group menus

Research

keywords

  • ATHEROGENIC DIET
  • ATHEROSCLEROSIS
  • GENE TRANSFER
  • MACROPHAGES
  • REVERSE TRANSCRIPTASE-PCR
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci118098

PubMed ID

  • 7635947
scroll to property group menus

Additional Document Info

start page

  • 1118

end page

  • 1124

volume

  • 96

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support