The Mechanism of Ciclosporin A Regulating the Expression of LOX-1 on Vascular Endothelium ofHyperlipidemic Rats

WU Hou-ke, WANG Wei, LI Hong.et al

Abstract

To observe the influence of Ciclosporin A (CsA) on the expression of lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1(LOX-1) on vascular endothelium of hyperlipidemic rats. Methods Hyperlipidemic rats model as for the study objects firstly were established. Then the high 〔5 mg/（kg·d）〕 and low〔1 mg/（kg·d）〕 dose of CsA were used to stimulate these rats, while the rats of normal blood lipids as control. After the end of intervention, the protein expressions of LOX-1 and C-reactive protein (CRP) on vascular endothelium of thoracic aorta were observed by Western blot and immunohistochemistry respectively. The serum levels of ox-LDL and reactive oxygen species (ROS) were also examined. Results An obviously up-regulated expression of LOX-1 on vascular endothelium of hyperlipidemic rats treated with CsA was observed (P<0.05), but not the serum level of ox-LDL (P>0.05). The further study result implied that CsA could increase the expression of CRP on vascular endothelial cells and serum level of ROS (P<0.05). Conclusion CsA can significantly up-regulate the expression of LOX-1 on vascular endothelium of hyperlipidemic rats through not only ox-LDL/LOX-1 pathway but also ROS/CRP pathway, which could cause the probability of occurrence of atherosclerosis.

 

Keywords: Ciclosporin A LOX-1, Hyperlipidemia CRP, ROS 

 

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References


Gusbeth-Tatomir P. Covic A. Causes and consequences of increased arterial stiffness in chronic kidney disease patients. Kidney Blood Press Res,2007;30(2):97-107.

Kubrich M. Petrakopoulou P. Kofler S. et al. Impact of coronary endothelial dysfunction on adverse long-term outcome after heart transplantation. Transplantation. 2008? 85 ( 11 ): 1580-1587.

Davies SW. Clinical presentation and diagnosis of coronary artery disease: stable angina. Hr Med Bull.2001;59:17-27. Labarrere CA. Abellada GC. Vascular anticoagulation and transplant coronary artery disease. Z Kardiol.2000;89(Suppl 9): IX/32-35.

Turkmen K, Tonbul HZ. Erdur KM. et al. Soluble TWEAK independently predicts atherosclerosis in renal transplant patients. BMC Nephrol. 2013? 14: 144. doi: 10. 1186/1471- 2369-14-144.

Turanlahti Ml, Taskinen M, Saarinen-Pihkala U. et al. Time- related arterial changes after allogeneic hematopoietic stem cell transplantation in children. Pediatr Res. 2013;73(6): 777-782.

Mitra S. Goyal T. Mehta JL. Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther. 2011 ;25(5):419-429.

Mitra S. Deshmukh A, Sachdeva R. et al. Oxidized low- density lii>oprotein and atherosclerosis implications in antioxidant therapy. Am J Med Sci,2011 ;342(2): 135-142.

Lu J. Mitra S. Wang X. et al. Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxid Redox Signal. 2011; 15(8) :2301-2333.

Taye A, El-Sheikh A A. Lectin-like oxidized low-density lipoprotein receptor 1 pathways. Eur J Clin Invest. 2013; 43 (7):740-745.

Pirillo A, Uboldi P. Kerri N. et al. Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins. Biochem Biophys Res Commun. 2012; 428(2);

230-233.

Gu L, Bai W, Li S. et al. Celastrol Prevents Atherosclerosis via Inhibiting LOX-l and Oxidative Stress. PLoS One» 2013; (6) :e65477.

Bao MH. Zhang YW. Zhou HH. Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-l/p38MAPK/NF-kappaB pathway. J Kthnopharmacol, 2013;46(2): 543-551.

Xu S. Ogura S. Chen J. et al. LOX-l in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci, 2013;70(16) :2859-2872.

Lu J. Mehta JL. LOX-l : a critical player in the genesis and progression of myocardial ischemia. Cardiovasc Drugs Ther. 2011;5(5) :431-440.

Boratynska M. Banasik M, Watorek E, et al. Influence of hypercholesterolemia and acute graft rejection on chronic nephropathy development in renal transplant recipients. Transplant Proc, 2003 ;35(6):2209-2212.

Wang W, Zhang P. Wang J, et al. Cyclosporine A aggravates vascular endothelial injury in hyperlipidemic rats by down- regulating decay-accelerating factor. Biochem Biophys Res Commun, 2009; 379(1) ;27-31.

Xu H, Duan J, Wang W, et al. Reactive oxygen species mediate oxidized low-density lipoprotein-induced endothelin-1 gene expression via extracellular signal-regulated kinase in vascular endothelial cells. J Hypertens.2008;26(5):956-963.

Abid MR, Spokes КС, Shih SC, et al. NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways. J Biol Chem, 2007; 282 ( 48 ): 35373- 35385.

Bellosillo В, Villamor N, Lopez-Guillermo A, et al. Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase- independent mechanism involving the generation of reactive oxygen species. Blood. 2001 ;98(9):2771-2777.


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