Journal Article

Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors

Lijing Jia, Masafumi Takahashi, Hajime Morimoto, Sadao Takahashi, Atsushi Izawa, Hirohiko Ise, Tadao Iwasaki, Hiroaki Hattori, Kou-Juey Wu and Uichi Ikeda

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 69, issue 2, pages 545-555
Published in print February 2006 | ISSN: 0008-6363
Published online February 2006 | e-ISSN: 1755-3245 | DOI:

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Objective: Sepsis accompanies myocardial dysfunction and dynamic alterations of cardiac metabolism. We have recently demonstrated that the very low-density lipoprotein receptor (VLDL-R), which is abundantly expressed in the heart, plays a key role in energy metabolism of the fasting heart. However, little is known about the function and regulation of the VLDL-R during sepsis. In the present study, we explored lipid accumulation and VLDL-R expression in the lipopolysaccharide (LPS)-stimulated heart in vivo and regulation of VLDL-R expression in vitro.

Methods and results: Electron microscopy and immunohistochemistry demonstrated that LPS significantly decreased both lipid accumulation and VLDL-R expression in the hearts of fasting mice. Treatment with LPS also downregulated VLDL-R in rat neonatal cardiac myocytes, and this downregulation was completely reversed by interleukin (IL)-1β receptor antagonist. IL-1β downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled β-VLDL but not DiI-labeled low-density lipoprotein (LDL). Use of specific pharmacologic inhibitors and short interference RNA revealed that Hsp90 was required for IL-1β to downregulate VLDL-R expression.

Conclusions: These findings suggest that IL-1β is a principle mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression.

Keywords: Cytokines; Inflammation; Lipoproteins; Myocytes; Receptors

Journal Article.  5768 words.  Illustrated.

Subjects: Cardiovascular Medicine