| First Author | Jia L | Year | 2006 |
| Journal | Cardiovasc Res | Volume | 69 |
| Issue | 2 | Pages | 545-55 |
| PubMed ID | 16376325 | Mgi Jnum | J:105715 |
| Mgi Id | MGI:3616371 | Doi | 10.1016/j.cardiores.2005.11.014 |
| Citation | Jia L, et al. (2006) Changes in cardiac lipid metabolism during sepsis: the essential role of very low-density lipoprotein receptors. Cardiovasc Res 69(2):545-55 |
| abstractText | 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)-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. |
