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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 545-555 |
| Number of pages | 11 |
| Journal | Cardiovascular research |
| Volume | 69 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2006 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Changes in cardiac lipid metabolism during sepsis : The essential role of very low-density lipoprotein receptors. / Jia, Lijing; Takahashi, Masafumi; Morimoto, Hajime; Takahashi, Sadao; Izawa, Atsushi; Ise, Hirohiko; Iwasaki, Tadao; Hattori, Hiroaki; Wu, Kou Juey; Ikeda, Uichi.
In: Cardiovascular research, Vol. 69, No. 2, 01.02.2006, p. 545-555.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Changes in cardiac lipid metabolism during sepsis
T2 - The essential role of very low-density lipoprotein receptors
AU - Jia, Lijing
AU - Takahashi, Masafumi
AU - Morimoto, Hajime
AU - Takahashi, Sadao
AU - Izawa, Atsushi
AU - Ise, Hirohiko
AU - Iwasaki, Tadao
AU - Hattori, Hiroaki
AU - Wu, Kou Juey
AU - Ikeda, Uichi
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=30744461626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30744461626&partnerID=8YFLogxK
U2 - 10.1016/j.cardiores.2005.11.014
DO - 10.1016/j.cardiores.2005.11.014
M3 - Article
C2 - 16376325
AN - SCOPUS:30744461626
VL - 69
SP - 545
EP - 555
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 2
ER -