HAN Yongkui, YUE Yunfei, ZHANG Kui, et al. GLP-1(7-36) inhibits atherosclerosis progression in ApoE-/- mouse aorta by lowering expressions of CD36 and ACAT1 in foam cells. [J]. Journal of Army Medical University 41(20):1947-1953(2019)
HAN Yongkui, YUE Yunfei, ZHANG Kui, et al. GLP-1(7-36) inhibits atherosclerosis progression in ApoE-/- mouse aorta by lowering expressions of CD36 and ACAT1 in foam cells. [J]. Journal of Army Medical University 41(20):1947-1953(2019) DOI: 10.16016/j.1000-5404.201905050.
GLP-1(7-36) inhibits atherosclerosis progression in ApoE-/- mouse aorta by lowering expressions of CD36 and ACAT1 in foam cells
Objective To investigate whether glucagon-like peptide-1(GLP-1)(7-36) inhibits the progression of aortic atherosclerotic plaque in ApoE knockout(ApoE
-/-
) mice fed with high-fat diet and the effect of GLP-1(7-36) on the expressions of CD36 and acyl-coenzyme A:cholesterol acyltransferase 1(ACAT1) in macrophage-derived foam cells. Methods Forty male ApoE
-/-
mice(6-8 weeks old
weighing 18-20 g) were randomized equally into normal diet group
high-fat diet(model) group
GLP-1(7-36) group
and GLP-1(7-36)+Exendin(9-39) group. The area of the atherosclerotic plaque in the aortic root of the mice was determined using HE staining
oil red O staining
and immunohistochemical staining with CD36 and ACAT1 antibodies. In the cell experiment
the macrophages(RAW264.7 cells) were induced with oxidized low-density lipoprotein(ox-LDL) and treated with different concentrations of GLP-1(7-36)
alone or in combination with Exendin(9-39). The expressions of CD36 and ACAT1 mRNAs and proteins in the cells was detected using RT-PCR and Western blotting
respectively. The levels of total cholesterol(TC)
free cholesterol(FC) and cholesterol ester(CE) in the cells were detected using high-performance liquid chromatography
and immunofluorescence analysis was performed to detect the expressions of CD36 and ACAT1 receptor proteins. Results Compared with the control mice
ApoE
-/-
mice on high-fat diet showed significantly higher expression levels of CD36 and ACAT1 at both the mRNA and protein levels in the aortic atherosclerotic plaques(P
<
0.05). CD36 and ACAT1 expressions in the plaques were significantly lowered by treatment of the mice with GLP-1(7-36)(P
<
0.05); the expression levels of CD36 and ACAT1 were significantly higher in GLP-1+Exendin group than in GLP-1 group(P
<
0.05). HE and oil red O staining showed that in the model group
the mean proportion of the plaque area in the aortic intimal area was(30.3±3.8)%
which was significantly lowered to(15.1±4.3)% in GLP-1 group(P
<
0.05); the ratio of the plaque area was(25.7±3.4)% in GLP-1+Exendin group
where significantly more numerous atherosclerotic plaques were observed below the intima as compared with GLP-1 group(P
<
0.05). GLP-1(7-36) significantly decreased the percentage of CD36-and ACAT1-positive cells in the aorta of the mice(P
<
0.05). Conclusion GLP-1 can reduce the accumulation of intracellular cholesterol by inhibiting the expression of CD36 and ACAT1 to suppress the foaming of macrophages
and thus inhibits the formation of atherosclerotic plaques.
Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3
Melatonin inhibits ox-LDL-induced proliferation of vascular smooth muscle cells
Effects of platelet microparticles on atherosclerotic plaque formation and stability in ApoE-/- mice
Sulforaphane inhibits hepatic steatosis in rats by down-regulating DGAT2 and ACAT1 expression
CD36 knockdown alleviates lipid accumulation induced by tumor necrosis factor-α and interleukin-6 in HepG2 cells
Related Author
ZHANG Ting
ZHOU Xi
WANG Xiaolan
SHEN Hui
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LIU Chuan
TANG Yang
KANG Huali
Related Institution
Department of Nutrition and Food Hygiene, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University)
Department of Cardiovascular Diseases, Second Affiliated Hospital, Army Medical University (Third Military Medical University)
Department of Cardiology, General Hospital of Central Theater
Third Military Medical University
Center of Drug Safety and Evaluation, Heilongjiang University of Chinese Medicine