Effects and mechanisms of nicotinic acid curcumin on apoptosis induced by low shear stress in human umbilical vein endothelial cells

doi:10.12092/j.issn.1009-2501.2018.08.003

Abstract

Abstract:

AIM: To investigate the effect of curcumin nicotinate（CN）on apoptosis of human umbilical vein endothelial cells (HUVECs) induced by low shear stress (LSS)and its mechanism. METHODS: A parallel plate flow chamber was used to establish a model of HUVECs apoptosis induced by low shear stress. Hoechst33258 fluorescence staining and flow cytometry were used to detect the effects of curcumin on the apoptosis of HUVECs. Western blot was used to detect the expression of proprotein convertase subtilisin/kexin type 9. RESULTS:Hoechst 33258 fluorescence staining showed that the number of HUVECs with apoptotic status in the LSS group was significantly higher than that in the static culture group. Compared with the LSS group, the HUVECs showing apoptotic status in the CN+LSS group were significantly reduced and showed a concentration-dependent manner. Among them, the least number of apoptotic cells was in 20 μmol/L CN+LSS group. Flow cytometry results showed that compared with the static culture group, the apoptosis rate of the LSS group was significantly increased, and the difference was statistically significant (P<0.01); compared with LSS group, the apoptosis rate of HUVECs in CN+LSS group was significantly reduced and showed a concentration-dependent manner. Among them, the decrease of apoptotic rate with 20 μmol/L CN+LSS group was the most obvious, the difference was statistically significant (P<0.01). Western blot results showed that compared with static culture group, PCSK9 protein expression was significantly increased in LSS group, and the difference was statistically significant (P<0.01). Compared with the LSS group, the expression of PCSK9 protein in the CN+LSS group was decreased and showed a concentrationdependent manner. The difference was statistically significant (P<0.05). Among them, the expression of PCSK9 protein was significantly decreased in 20 μmol/L CN+LSS group (P<0.01). CONCLUSION: CN inhibits the apoptosis of HUVECs induced by LSS, and its mechanism is related to down-regulation of the protein expression of PCSK9 in HUVECs under the action of LSS.

Key words: atherosclerosis, niacin curcumin esters, low shear stress, human umbilical vein endothelial cells, cell apoptosis, PCSK9

CLC Number:

R965.2

References

［1］Choy JC, Granville DJ, Hunt DW, et al. Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis［J］. J Mol Cell Cardiol, 2001,33(9):1673-1690.
［2］Tada S, Dong C, Tarbell JM. Effect of the stress phase angle on the strain energy density of the endothelial plasma membrane［J］. Biophys J, 2007,93(9):3026-3033.
［3］Sheng X, Liu Y, Wang J, et al. HUVECs respond to low shear stress stimulation by activating Wnt/beta-catenin signaling pathway［J］. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2017,33(12):1657-1661.
［4］Tricot O, Mallat Z, Heymes C, et al. Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques［J］. Circulation, 2000,101(21):2450-2453.
［5］Li J, Liang X, Wang Y, et al. Investigation of highly expressed PCSK9 in atherosclerotic plaques and ox-LDL-induced endothelial cell apoptosis［J］. Mol Med Rep, 2017,16(2):1817-1825.
［6］龚勇珍, 姚海伦, 孙少卫, 等. SREBP-1/小凹蛋白1介导烟酸姜黄素酯对ApoE~(-/-)小鼠的抗动脉粥样硬化作用［J］. 中国动脉硬化杂志, 2014,22(12):1189-1194.
［7］阳巍. 烟酸姜黄素酯对血管平滑肌细胞增殖的影响及机制研究［D］. 南华大学, 2013.
［8］Hansson GK. Inflammation, atherosclerosis, and coronary artery disease［J］. N Engl J Med, 2005,352(16):1685-1695.
［9］McMillan DE. Blood flow and the localization of atherosclerotic plaques［J］. Stroke, 1985,16(4):582-587.
［10］Peiffer V, Sherwin SJ, Weinberg PD. Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review［J］. Cardiovasc Res, 2013,99(2):242-250.
［11］游云, 张毅, 廖福龙, 等. 丹参酮Ⅱa血管外膜给药改善低血流剪应力诱导的血管内膜损伤［J］. 微循环学杂志, 2012,22(2):84.
［12］周淑媛, 王迎寒, 李玉洁, 等. 参莲提取物对兔颈总动脉低剪应力模型血流及血管病理形态的影响［J］. 中国中药杂志, 2013,38(10):1595-1600.
［13］周淑媛. 低切应力对血管内皮屏障功能的调控及SL提取物的干预机制［D］. 中国中医科学院, 2013.
［14］于长安, 温见燕, 廖福龙. 剪应力与姜黄素联合作用对人脐静脉内皮细胞功能的影响［J］. 中国病理生理杂志, 2010,26(10):1968.
［15］刘承, 钟毅, 冯健, 等. 姜黄素抗动脉粥样硬化及其危险因素的作用与机制回顾［J］. 中药新药与临床药理, 2017,28(2):257-262.
［16］阳巍, 廖端芳, 庹勤慧. 姜黄素抗动脉粥样硬化研究进展［J］. 国际病理科学与临床杂志, 2012,32(1):55-58.
［17］Qin L, Yang YB, Tuo QH, et al. Effects and underlying mechanisms of curcumin on the proliferation of vascular smooth muscle cells induced by Chol:MbetaCD［J］. Biochem Biophys Res Commun, 2009,379(2):277-282.
［18］张波, 刘宏斌. 烟酸抑制血管紧张素II诱导的内皮细胞凋亡［J］. 临床和实验医学杂志, 2012,11(10):731-733.
［19］杨冬梅, 阳巍, 邱飞, 等. 姜黄素烟酸酯对血管平滑肌细胞增殖及ERK1/2信号通路的影响［J］. 中国药理学通报, 2016,32(11):1526-1530.
［20］Maxwell KN, Soccio RE, Duncan EM, et al. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterolfed mice［J］. J Lipid Res, 2003,44(11):2109-2119.
［21］Norata GD, Tavori H, Pirillo A, et al. Biology of proprotein convertase subtilisin kexin 9: beyond low-density lipoprotein cholesterol lowering［J］. Cardiovasc Res, 2016,112(1):429-442.
［22］Zhao XS, Wu Q, Peng J, et al. Hyperlipidemiainduced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression［J］. Mol Med Rep, 2017,15(2):712-718.
［23］Kysenius K, Muggalla P, Matlik K, et al. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling［J］. Cell Mol Life Sci, 2012,69(11):1903-1916.
［24］Gan SS, Ye JQ, Wang L, et al. Inhibition of PCSK9 protects against radiation-induced damage of prostate cancer cells［J］. Onco Targets Ther, 2017,10:2139-2146.
［25］Bai J, Na H, Hua X, et al. A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition［J］. Oncotarget, 2017,8(4):6929-6939.
［26］Piao MX, Bai JW, Zhang PF, et al. PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways［J］. Int J Clin Exp Pathol, 2015,8(3):2787-2794.
［27］Wu CY, Tang ZH, Jiang L, et al. PCSK9 siRNA inhibits HUVEC apoptosis induced by ox-LDL via Bcl/Bax-caspase9-caspase3 pathway［J］. Mol Cell Biochem, 2012,359(12):347-358.
［28］张彩平, 孙少卫, 龚勇珍, 等. PCSK9/LDLR通路介导姜黄素烟酸酯促进HepG2摄取脂质［J］. 生物化学与生物物理进展, 2015,42(9):825-832.

[1]	ZHAO Lingzhi, HE Yanjun, XIE Jianqin, YOU Chongge. Research progress on therapeutic role of recombinant human soluble thrombomodulin in atherosclerosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(7): 832-840.
[2]	ZHANG Xuejiao, LIU Jieting, LI Luxin, CHEN Peijian, DING Minglu, SUN Mengwei, CHU Yanhui, ZHANG Zhen . Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 257-265.
[3]	LI Junmin, NIU Hengli, XIE Mingquan, SU Jinlong. Effects of hawthorn flavonoids on atherosclerotic and hyperlipidemia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 276-282.
[4]	WANG Ruijie, WANG Liang, XU Dan, ZHOU Miaomiao, LI Jiming. Effects of PCSK9 inhibitors on blood lipids and inflammatory factors in patients with coronary heart disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(4): 409-417.
[5]	GUAN Li, CHEN Wu, SUN Junfang, LI Wei. Xintahua water extract improves the disease indexes of atherosclerosis model rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(1): 18-23.
[6]	LI Mengying, SI Mingdong, WEN Zishuai, SHI Huan, LI Xinrui, ZHANG Yuanyuan, WANG Hongfang, MA Donglai, CHU Li. Mechanism of saffron in treating atherosclerosis based on network pharmacology method [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 649-657.
[7]	XIE Xiangmei, HUANG Zhihong, LIU Xiaoju, XUE Bing, LAN Baozhu. Effects of atorvastatin and folic acid tablets on homocysteine and carotid atherosclerosis in patients with type H hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(4): 455-459.
[8]	YIN Qing, DU Rongzeng. Research advances of mechanically sensitive ion channel Piezo1 in cardiovascular diseases#br# [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(12): 1414-1421.
[9]	LI Tianxiang, LI Sujuan, HAO Xiangyu, ZHU Zhibo, GUO Jianqiang. Effects of telmisartan on intestinal flora and its metabolite TMAO in atherosclerosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(11): 1233-1241.
[10]	QUAN Haiyan, LIU Yuhuan, YANG Li, YANG Fang, QIN Xuping. Improvement of CGRP on vascular endothelial cells insulin resistance via activation of cAMP/PPARγ/eNOS pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(6): 615-622.
[11]	GUAN Qiaobing，YANG Yi，GUO Li，HAN Chenyang. NBP inhibits ox-LDL induced apoptosis of endothelial cells through endoplasmic reticulum stress pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(4): 397-402.
[12]	ZHENG Xiao, HU Xiaosheng. Effects of rosuvastatin on hypertension with carotid atherosclerosis and its influence on peripheral macrophage polarization [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(9): 1035-1039.
[13]	LIU Zhengdong, ZHENG Ning. Correlation of TMAO and Lp-PLA2 levels in patients with atherosclerotic ischemic stroke [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(6): 684-688.
[14]	MA Chenghua, ZHOU Haijing, SHI Wen, WANG Zhiqiang, YANG Lan, CHEN Ping, ZHENG Xueli, MA Rui, MA Lijuan. Mechanism of apoptosis of mucoepidermoid carcinoma MEC-1 cells induced by ethanol extract of Lamiophlomis rotate [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(3): 253-259.
[15]	LUO Ziyin, XIANG Bingqian, GAO Hui, QIU Xiaoxiao, QIAN Xiaoying, WANG Wantie. Effects of dexmedetomidine on JNK in A549 cells with hypoxia/reoxygenation injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1346-1351.