Xi Wu1, Yuan Lü1, Kun Fu1, Shaoping Wang1, Donghui Zhao1, Hongyu Peng1, Qian Fan1, Yun Lü1, Mankun Xin1, Jinghua Liu2. 1. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. 2. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. Email: liujinghua@vip.sina.com.
Abstract
OBJECTIVE: To explore the effects and related mechanisms of exogenous fibroblast growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. METHODS: Male 17-week-old C57BL/6J mice and apoE-/- mice were randomly divided into three groups (n = 12 each): blank control group (C vehicle), atherosclerosis group without FGF21 (apoE-/- vehicle) and apoE-/- plus FGF21 (100 µg × kg⁻¹ × d⁻¹ subcutaneously treatment) . All mice were fed with high-fat diet for 4 weeks. After 4 weeks treatments, atherosclerotic lesions in aortic arch and inner diameter of abdominal aorta were measured by ultrasonography. Plasma lipid profiles, CRP and TNFα were measured. The whole aorta and aortic root were prepared for HE and oil red O staining to analyze lesion areas. RESULTS: There was no evident plaque in C vehicle group. TC/HDL-C, LDL-C/HDL-C, non-HDL-C, expression of CRP and TNFα were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). IMT of aorta [(156.4 ± 17.6)µm vs. (57.8 ± 7.4)µm] were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). While FGF21 significantly reduced the lesion area in aorta arch [(1.42 ± 0.16) mm² vs. (2.30 ± 0.10) mm², P < 0.05] and the inner diameter of abdominal aorta [(0.97 ± 0.03) mm vs. (0.75 ± 0.18) mm, P < 0.05] compared to apoE-/- vehicle group. Similarly, TC/HDL-C(5.11 ± 0.70), LDL-C/HDL-C(3.90 ± 0.76), non-HDL-C[(6.33 ± 1.22)mmol/L], plasma CRP[(4.20 ± 1.03)mmol/L] and plasma TNFα[(1.29 ± 0.47)mmol/L] were also reduced by FGF21( all P < 0.05 vs. apoE-/- vehicle). Moreover, FGF21 decreased the IMT[(107.2 ± 33.5)µm vs. (156.4 ± 17.6)µm], lesion area of aorta [(14.26 ± 3.5)%] vs. [(23.06 ± 4.16)%] and plaque size of aorta root [(21.75 ± 7.14)% vs. (38.03 ± 5.76)%] (all P < 0.05 vs. apoE-/- vehicle). CONCLUSIONS: FGF21 can protect apoE-/- mice from atherosclerosis by modifying lipid profiles and downregulating CRP and TNFα expressions.
OBJECTIVE: To explore the effects and related mechanisms of exogenous fibroblast growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-)mice. METHODS: Male 17-week-old C57BL/6J mice and apoE-/- mice were randomly divided into three groups (n = 12 each): blank control group (C vehicle), atherosclerosis group without FGF21 (apoE-/- vehicle) and apoE-/- plus FGF21 (100 µg × kg⁻¹ × d⁻¹ subcutaneously treatment) . All mice were fed with high-fat diet for 4 weeks. After 4 weeks treatments, atherosclerotic lesions in aortic arch and inner diameter of abdominal aorta were measured by ultrasonography. Plasma lipid profiles, CRP and TNFα were measured. The whole aorta and aortic root were prepared for HE and oil red O staining to analyze lesion areas. RESULTS: There was no evident plaque in C vehicle group. TC/HDL-C, LDL-C/HDL-C, non-HDL-C, expression of CRP and TNFα were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). IMT of aorta [(156.4 ± 17.6)µm vs. (57.8 ± 7.4)µm] were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). While FGF21 significantly reduced the lesion area in aorta arch [(1.42 ± 0.16) mm² vs. (2.30 ± 0.10) mm², P < 0.05] and the inner diameter of abdominal aorta [(0.97 ± 0.03) mm vs. (0.75 ± 0.18) mm, P < 0.05] compared to apoE-/- vehicle group. Similarly, TC/HDL-C(5.11 ± 0.70), LDL-C/HDL-C(3.90 ± 0.76), non-HDL-C[(6.33 ± 1.22)mmol/L], plasma CRP[(4.20 ± 1.03)mmol/L] and plasma TNFα[(1.29 ± 0.47)mmol/L] were also reduced by FGF21( all P < 0.05 vs. apoE-/- vehicle). Moreover, FGF21 decreased the IMT[(107.2 ± 33.5)µm vs. (156.4 ± 17.6)µm], lesion area of aorta [(14.26 ± 3.5)%] vs. [(23.06 ± 4.16)%] and plaque size of aorta root [(21.75 ± 7.14)% vs. (38.03 ± 5.76)%] (all P < 0.05 vs. apoE-/- vehicle). CONCLUSIONS:FGF21 can protect apoE-/- mice from atherosclerosis by modifying lipid profiles and downregulating CRP and TNFα expressions.