| RRC ID |
49602
|
| Author |
Fang Q, Wang J, Zhang Y, Wang L, Li W, Han J, Huang W, Liang G, Wang Y.
|
| Title |
Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.
|
| Journal |
Biochim Biophys Acta Mol Basis Dis
|
| Abstract |
Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling.
|
| Volume |
1864(1)
|
| Pages |
252-262
|
| Published |
2018-1-1
|
| DOI |
10.1016/j.bbadis.2017.09.026
|
| PII |
S0925-4439(17)30352-6
|
| PMID |
28965884
|
| MeSH |
Animals
Animals, Newborn
Cardiomegaly / pathology
Cardiomegaly / prevention & control
Cardiomyopathies / etiology
Cardiomyopathies / prevention & control*
Cardiotonic Agents / pharmacology*
Cells, Cultured
Chalcones / pharmacology*
Diet, High-Fat
Fibrosis / prevention & control
Heart / drug effects*
Lymphocyte Antigen 96 / antagonists & inhibitors*
Lymphocyte Antigen 96 / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / pathology*
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology
Obesity / complications*
Rats
|
| IF |
4.328
|
| Times Cited |
4
|
| Resource |
| Mice |
RBRC02388 |
