TSB2 inhibits atherosclerosis by reducing the production of superoxide anion of uncoupled endothelial nitric oxide synthase

Home > Archive>Volume 31, Issue 10, 2023 >833-840

TSB2 inhibits atherosclerosis by reducing the production of superoxide anion of uncoupled endothelial nitric oxide synthase
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                        WU Fangyuan1,2WU Fangyuan
Division of Hypertension and Vascular Diseases, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China;National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China
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LI Yan2,3LI Yan
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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NING Dasheng2,3NING Dasheng
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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CHEN Jing1,2CHEN Jing
Division of Hypertension and Vascular Diseases, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China;National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China
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LI Shangxuan1,2LI Shangxuan
Division of Hypertension and Vascular Diseases, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China;National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China
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PENG Yueming2,3PENG Yueming
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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HE Shihui2,3HE Shihui
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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YAN Fengxia2,3YAN Fengxia
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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OU Jingsong2,3OU Jingsong
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
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OU Zhijun1,2OU Zhijun
Division of Hypertension and Vascular Diseases, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China;National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation Sun Yat-sen University & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China
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Affiliation:1.Division of Hypertension and Vascular Diseases, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China;2.National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University) & Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases & Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong 510080, China;3.Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China)
Clc Number:R363;R5
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Abstract:

Aim To observe the effect of TSB2 inhibiting the combination of heat shock protein 90 (HSP90) and endothelial nitric oxide synthase (eNOS) on the formation of atherosclerosis. Methods Human umbilical vein endothelial cells (HUVEC) were treated with TSB2 and the combination between HSP90 and eNOS was detected by co-immunoprecipitation. C57BL/6 mice and low density lipoprotein receptor knockout (LDLR－/－) mice were fed with normal diet (ND) or high fat diet (HFD) for 12 weeks while injected with phosphate buffered saline (PBS) or TSB2 intraperitoneally. The mice were divided into four groups:C57BL/6＋ ND＋PBS group, LDLR－/－＋ND＋PBS group, LDLR－/－＋HFD＋PBS group, LDLR－/－＋HFD ＋TSB2 group. Then the aorta was isolated. The combination between HSP90 and eNOS in aorta was measured. The atherosclerotic plaque in aorta and aortic sinus were determined. The production of nitric oxide (NO) and superoxide anion (O₂·－) were also detected. At the same time, L-monomethyl-arginine (L-NMMA), a competitive substrate of L-arginine, was used to determine the production of NO, and L-nitroarginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, was used to determine the production of O₂·－. Results Compared with control group, the combination between HSP90 and eNOS was decreased by 41.06% (P＜0.05) in cultured HUVEC treated with TBS2. Compared with LDLR－/－＋HFD＋PBS group,the combination between HSP90 and eNOS in the mouse aortas was decreased by 40.95% (P＜0.05) in LDLR－/－＋HFD＋TSB2 group, and the production of O₂·－ was decreased by 63.73% (P＜0.05) (L-NAME significantly inhibited the production of O₂·－ in LDLR－/－＋HFD＋PBS group), while the production of NO had no significant change in the mouse aortic endothelial cells (L-NMMA inhibited NO production in all groups), and the formation of atherosclerotic lesions in aortas and aortic sinus were significantly decreased by 59.39% and 68.86% (P＜0.05) respectively in LDLR－/－＋HFD＋TSB2 group. Conclusion TSB2 can reduce the O₂·－ production of uncoupled eNOS in vascular endothelial cells by inhibiting the combination of HSP90 and eNOS in aortic endothelial cells, and finally inhibits the formation of atherosclerosis.

Key words:atherosclerosis; vascular endothelial cells; endothelial nitric oxide synthase; heat shock protein 90

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WU Fangyuan, LI Yan, NING Dasheng, CHEN Jing, LI Shangxuan, PENG Yueming, HE Shihui, YAN Fengxia, OU Jingsong, OU Zhijun. TSB2 inhibits atherosclerosis by reducing the production of superoxide anion of uncoupled endothelial nitric oxide synthase[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2023,31(10):833-840.

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Received:June 29,2022
Revised:February 19,2023
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Online: November 08,2023
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