Protective effect of growth differentiation factor 11 on aorta in ApoE-/-mice fed with high-fat diet / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the effect of growth differentiation factor 11 ( GDF11 ) on aorta in apolipoprotein E-Null( ApoE-/-) mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups:vehicle group(n=10), GDF11 group (n=10),adeno-associated virus-green fluorescent protein group(AAV-GFP group, n=10), and AAV-GDF11 group ( n=10 ) . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 (IL-6), tumor necrosis factor-α( TNF-α), total cholesterol ( TC), triglycerides ( TG), oxidized low density lipoprotein(ox-LDL), and free fatty acids(FFA)levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group : GDF11 group:(31. 23 ± 3. 12)% vs (17. 18 ± 2. 17) %;AAV-GFP group : AAV-GDF11 group:(38.01±4.43)% vs(14.54±2.86)%,P<0.05]andcrosssections[Vehiclegroup :GDF11 group:(19. 87 ± 2. 11)% vs (10. 32 ± 1. 47)%;AAV-GFP group : AAV-GDF11 group:(23. 02 ± 2. 76)%vs (9.06±1.63)%, P<0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic lesion in ApoE-/-mice, which may be involved in endothelial protection, such as to reduce inflammatory reaction, and to change cellular composition in plaques.