1.Effects and mechanism of fibroblast growth factor 21 on rat vascular smooth muscle cells calcification.
Kun FU ; Yi XIN ; Yuchen SHI ; Xuwei ZHENG ; Yuan LYU ; Zhenye XU ; Jinghua LIU ; Email: LIUJINGHUA@VIP.SINA.COM.
Chinese Journal of Cardiology 2015;43(10):879-886
OBJECTIVETo observe the effect and mechanism of fibroblast growth factor 21 (FGF21) on rat vascular smooth muscle cells (VSMCs) calcification in vitro.
METHODSVSMCs was treated with calcification medium containing calcium chloride and β-glycerophosphate to induce rat VSMCs calcification in vitro. VSMCs were divided into 5 groups: the control group (cultured in normal medium), the calcification group (incubated in calcified medium), the FGF21 group (cultured in calcified medium and FGF21), the PD166866 group (cultured in calcified medium and FGF21 and PD166866, inhibitor of fibroblast growth factor receptor-1 (FGFR1)), the GW9662 group (cultured in calcified medium and FGF21 and GW9662, inhibitor of peroxisome proliferators activated receptor-γ (PPAR-γ)). The calcification of VSMCs was detected by calcium content, alkaline phosphatase activity and alizarin red staining. The protein and mRNA expression of FGFR1, β-Klotho, osteocalcin and smooth muscle 22α (SM22α) were determined by western blot analysis and realtime-PCR, respectively.
RESULTS(1) The mRNA (P < 0.01) and protein expressions of β-Klotho and FGFR1 were significantly downregulated in calcification group compared with control group (P < 0.05 or 0.01). (2) The protein levels and mRNA expression of calcium content, alkaline phosphatase activity and osteocalcin were significantly downregulated, while the protein levels and mRNA of SM22α were significantly increased in FGF21 group compared with calcification group (all P < 0.05). Moreover, alizarin red staining verified positive red nodules on calcified VSMCs was significantly reduced in FGF21 group than in calcification group. (3) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between PD166866 group and calcification group (all P > 0.05). (4) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between GW9662 group and calcification group (all P > 0.05).
CONCLUSIONThe inhibition of VSMCs calcification by FGF21 is mediated by further downregulating FGFR1 and β-Klotho while activating PPAR-γ pathways.
Animals ; Calcium ; Fibroblast Growth Factors ; Glycerophosphates ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Rats ; Vascular Calcification
2.Association of atherosclerotic renal artery stenosis with major adverse cardiovascular events after acute myocardial infarction.
Bin ZHENG ; Jinghua LIU ; Qin MA ; Donghui ZHAO ; Xin WANG ; Ze ZHENG
Chinese Medical Journal 2014;127(4):618-622
BACKGROUNDPatients with atherosclerotic renal artery stenosis (ARAS) are in substantial risk of cardiovascular adverse events. We investigated whether myocardial infarction patients with ARAS are in additional risk of cardiovascular events.
METHODSIn this retrospective study, 257 patients with type 1 myocardial infarction were enrolled. Median follow-up was 42 months. Composite endpoint events are analyzed by definitions of ARAS as ≥ 50% or ≥ 70% diameter stenosis.
RESULTSDefining ARAS as ≥ 70% diameter stenosis, ARAS was a significant predictor for composite endpoint events including death, non-fatal myocardial infarction, ischaemic stroke and intracranial haemorrhage, rehospitalisation for cardiac failure (HR: 4.381; 95% CI: 1.770-10.842) by Cox regression analysis, but not for death. Diabetes mellitus was also a significant predictor for composite endpoint events (HR: 2.756; 95% CI: 1.295-5.863). However, defining ARAS ≥ 50% diameter stenosis, ARAS was no longer a significant predictor for composite endpoint events or death.
CONCLUSIONSAlthough not associated with mortality, ARAS ≥ 70% is associated with major adverse cardiac events after acute myocardial infarction. For prognosis, ≥ 70% diameter stenosis is a more appropriate criteria for ARAS definition than ≥ 50% diameter stenosis.
Atherosclerosis ; pathology ; Cardiovascular Diseases ; etiology ; Diabetes Complications ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; complications ; Renal Artery Obstruction ; complications ; pathology ; Retrospective Studies
3.Impact of exogenous fibroblast growth factor 21 on atherosclerosis in apolipoprotein E deficient mice.
Xi WU ; Yuan LÜ ; Kun FU ; Shaoping WANG ; Donghui ZHAO ; Hongyu PENG ; Qian FAN ; Yun LÜ ; Mankun XIN ; Jinghua LIU
Chinese Journal of Cardiology 2014;42(2):126-131
OBJECTIVETo explore the effects and related mechanisms of exogenous fibroblast growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-) mice.
METHODSMale 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.
RESULTSThere 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).
CONCLUSIONSFGF21 can protect apoE-/- mice from atherosclerosis by modifying lipid profiles and downregulating CRP and TNFα expressions.
Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; Atherosclerosis ; blood ; pathology ; prevention & control ; C-Reactive Protein ; metabolism ; Disease Models, Animal ; Fibroblast Growth Factors ; pharmacology ; Lipids ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic ; pathology ; Tumor Necrosis Factor-alpha ; metabolism