Effect of endothelial cell-derived exosomes on immune factors in atherosclerotic rats
LUO Xueting1 ZHOU Yong2 JIANG Manhong2 LUO Baoping1
1.The First Clinical College, Hubei University of Chinese Medicine，Hubei Province, Wuhan 430000, China;
2.Department of Oncology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Province, Wuhan 430000, China
Abstract：Objective To investigation the effect of vascular endothelial cells derived exosomes on the immune response and inflammatory damage mechanism in atherosclerotic rats. Methods Vascular endothelial cells derived exosomes were cultivated and identified. Thirty Wistar rats were divided into three groups according to the random digital table method, including the control, model and immune groups, 10 rats in each group. The latter two groups were used to establish atherosclerotic models, and the immune group was injected with exosomes at the fifth week of feeding. Vascular endothelial cells were separated from rat serum at the eighth week to detect the biochemical criterion [blood glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], mRNA expression of cytokine [interleukin-2 (IL-2), interleukin-4 (IL-4), γ-interferon (IFN-γ)] and expression levels of inflammatory factor [tumor necrosis factor (TNF-α), interleukin-1 (IL-1), endothelin-1 (ET-1) and nitric oxide (NO)]. Results Vascular endothelial cells and rat model were established successfully. Compared with the control group, the differences of blood glucose, TG, TC, HDL-C, LDL-C in the model group were highly statistically significant (P < 0.01). The TG, TC and LDL-C of the immune group were lower than those of the model group (P < 0.05 or P < 0.01). Compared with the control group, the levels of cytokines, TNF-α, IL-1 and ET-1 were significantly increased and the level of serum NO was significantly decreased after the modeling (P < 0.01). Compared with the model group, the levels of cytokines, TNF-α, IL-1 and ET-1 in the immune group were significantly decreased, and the serum NO level was significantly increased (P < 0.05 or P < 0.01). The number of peripheral blood endothelial cells in the model group was significantly increased under the microscope. The number of peripheral blood endothelial cells in the immue group had slight increase, but was than that in the model group. Conclusion In the pathological process of atherosclerosis, vascular endothelial cells derived exosomes may protect the damaged endothelial cells, alleviate immune response and inflammatory damage, and reduce the clinical indicators.
[1] Jeong IK，Kim SG，Cho DH，et al. Impact of carotid athe-rosclerosis detection on physician and patient behavior in the management of type 2 diabetes mellitus：a prospective，observational，multicenter study [J]. BMC Cardiovasc Disord，2016，16（1）：220-225.
[2] Barker G，Parnell E，van Basten B，et al. The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation [J]. J Cardiovasc Dev Dis，2017， 5（4）：4-9.
[3] Li C，Yang L，Wu H，et al. Paeonol Inhibits Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial Cells Autophagy by Upregulating the Expression of miRNA-30a [J]. Front Pharmacol，2018，8（9）：95-99.
[4] Zrelli H，Kusunoki M，Miyazaki H. Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo Synthesis and Stabilization [J]. Phytother Res，2015，29（7）：1011-1018.
[5] Yu XQ，He Y，Lu J，et al. Study on detection methods for auramine O in Chinese patent medicine [J]. Chinese Journal of Pharmaceutical Analysis，2014，34（1）：130-135.
[6] Brunetti ND，Salvemini G，Cuculo A，et al. Coronary artery ectasia is related to coronary slow flow and inflammatory activation [J]. Atherosclerosis，2014，233，（2）：636-640．
[7] Zhang G，Yang P. A novel cell-cell communication mechanism in the nervous system：exosomes [J]. J Neurosci Res，2018，96（1）：45-52.
[8] 邢玉桂，马飞，孙洪胜，大鼠动脉粥样硬化模型的建立[J].药学研究，2015，4（34）：192-195.
[9] Bengtson LG，Chen LY，Chamberlain AM，et al. Temporal trends in the occurrence and outcomes of atrial fibrillation in patients with acute myocardial infarction （from the Atherosclerosis Risk in Communities Surveillance Study） [J]. Am J Cardiol，2014，114（5）：692-697.
[10] Song K，Li L，Sun G，et al. MicroRNA-381 regulates the occurrence and immune responses of coronary atherosclerosis via cyclooxygenase-2 [J]. Exp Ther Med，2018，15（5）：4557-4563.
[11] Elwany S，Ibrahim AA，Soliman AI，et al. The significance of atherosclerosis in hypertensive patients with epistaxis[J]. J Laryngol Otol，2018，132（4）：323-326.
[12] Márk L，Harangi M，Paragh G. The labyrinth of residual risk：reduction of the remaining lipid and inflammation risk in the prevention of atherosclerosiss [J]. Orv Hetil，2018，159（4）：124-130.
[13] Lopes-Virella MF，Carter RE，Baker NL，et al. High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes [J]. Nephrol Dial Transplant，2012，27（4）：1416-1423.
[14] Lopes-Virella MF，Hunt KJ，Baker NL，et al. The levels of MDA-LDL in circulating immune complexes predict myocardial infarction in the VADT study [J]. Atherosclerosis，2012，224（2）：526-531.
[15] Lopes-Virella MF，Hunt KJ，Baker NL，et al. High levels of AGE-LDL，and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes [J]. J Diabetes Complications，2016，30（4）：693-699.
[16] Greening DW，Gopal SK，Xu R，et al. Exosomes and their roles in immune regulation and cancer [J]. Semin Cell Dev Biol，2015，4（40）：72-81.
[17] Frydrychowicz M，Kolecka-Bednarczyk A，Madejczyk M，et al. Exosomes-structure，biogenesis and biological role in non-small-cell lung cancer [J]. Scand J Immunol，2015， 81（1）：2-10.
[18] Pérez-Boza J，Lion M，Struman I. Exploring the RNA landscape of endothelial exosomes [J]. RNA，2018，24（3）：423-435.
[19] Madden JA． Ｒole of the vascular endothelium and plaque inacute ischemic stroke [J]. Neurology，2012，79（l1）：S58-S62．
[20] Caldirola MS，Rodríguez Broggi MG，et al. Primary Immunodeficiencies Unravel the Role of IL-2/CD25/STAT5b in Human Natural Killer Cell Maturation [J]. Front Immunol，2018，22（9）：1429-1435.
[21] Parker D，Sloane R，Pieper CF，et al. Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood [J]. J Gerontol A Biol Sci Med Sci，2018， 22（9）：192-203.
2019, Vol. 16 
京公网安备 11010502046598号