Changes in cardiac lipid metabolism during sepsis: the essential role of very low-density lipoprotein receptors.
Cardiovasc Res
; 69(2): 545-55, 2006 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-16376325
ABSTRACT
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 ANDRESULTS:
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)-1beta receptor antagonist. IL-1beta downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled beta-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-1beta to downregulate VLDL-R expression.CONCLUSIONS:
These findings suggest that IL-1beta is a principle mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de LDL
/
Sepsis
/
Metabolismo de los Lípidos
/
Miocardio
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cardiovasc Res
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón