MD1 deficiency increases the susceptibility to ventricular arrhythmia in obese mice by activating the TLR4 / MyD88 signaling pathway
Author:
Affiliation:

Department of Cardiology, Zhengzhou Seventh People’s Hospital, Zhengzhou 450000, China

Clc Number:

R-33

Fund Project:

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    Objective To investigate effects of MD1 deficiency on the susceptibility of obese mice to ventricular arrhythmias and the mechanism involved. Methods Sixteen MD1-knockout (KO) mice and 16 male wild type (WT) mice were divided into WT normal group, MD1-ko- normal group, WT high fat group and MD1-ko- high fat group. The high fat groups were fed a high-fat diet (fat energy accounted for 60%) for 20 weeks, and the normal groups were fed a normal diet (fat energy accounted for 10%). The body weight (BW), heart weight ( HW), blood glucose level, total cholesterol, triglyceride and low-density lipoprotein ( LDL) cholesterol levels, and HW/ BW ratio of the mice were measured. RR spacing, PR spacing, QRS duration, QTc interval, LVEDd, LVEDs, LVFS, and LVEF were measured by electrocardiography and echocardiography. Western blot was used to analyze TLR4, MyD88, P-CAMKII, Collagen I, Collagen III and TGF-β1 protein levels. Cardiac hypertrophy and fibrosis were observed in mice by HE staining and PSR staining. Results The body index, blood glucose, total cholesterol, triglyceride, LDL cholesterol, QTc interval, LVEDd, LVEDs, LVFS, and LVEF were significantly higher in the MD1-ko- high fat group than in the WT high fat group (P < 0. 05). Furthermore, the action potential duration ( APD20, APD50, APD90) of the MD1-ko- high fat group was significantly higher than that of the WT high fat group (P <0. 05), and he APD alternating threshold of the MD1-ko- high fat group was significantly higher than that of the WT high fat group (P< 0. 05). The arrhythmia ratio of the MD1-ko- high fat group was significantly higher than that of the WT high fat group (P < 0. 05). The expression of TLR4, MyD88, and P- CAMKII in the MD1-ko- high fat group was significantly higher than that in the WT high fat group (P < 0. 05). The HW/ BW ratio in the MD1-ko- high fat group (7. 59 ± 0. 78) was significantly higher than that in the WT high fat group (6. 07 ± 0. 58; P < 0. 05). The Gross hearts of the MD1-ko- high fat group (381. 23 ± 35. 76) μm2was significantly higher than that of the WT high fat group (190. 15 ± 25. 23) μm2 ; P < 0. 05). Finally, the protein expression of Collagen I, Collagen III, and TGF-β1 in the MD1-ko- high fat group was significantly higher than that in the WT high fat group (P< 0. 05). Conclusions MD1 deficiency increases the susceptibility to high-fat-diet-induced arrhythmias, mainly because of enhanced activation of the TLR4 / MyD88 signaling pathway, leading to left ventricular hypertrophy and fibrosis, which increases the expression of TLR4 / MyD88 signaling pathway-related proteins.

    Reference
    Related
    Cited by
Get Citation
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
History
  • Received:November 13,2019
  • Revised:
  • Adopted:
  • Online: July 23,2020
  • Published: