Effect of GDF-15/GFRAL pathway on progression of atherosclerosis in mice
10.3969/j.issn.1009-0126.2024.09.021
- VernacularTitle:生长分化因子15与胶质源性神经营养因子样受体通路对小鼠动脉粥样硬化进展的影响
- Author:
Hunan XIAO
1
;
Benchuan HAO
;
Lü LÜ
;
Yulun CAI
;
Xiaofan WANG
;
Hongbin LIU
Author Information
1. 100853 北京,解放军总医院第二医学中心心血管内科国家老年疾病临床研究中心
- Keywords:
atherosclerosis;
models,animal;
growth differentiation factor 15;
glial cell line-derived neurotrophic factor receptors;
lipid metabolism
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(9):1079-1083
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P＜0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P＜0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P＜0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P＜0.05),lighter plaque burden[(22.22±2.58)％vs(31.61±3.51)％,P＜0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P＜0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P＜0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P＜0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.
