Alpha-lipoic acid increases circulating endothelial progenitor cells in newly diagnosed type 2 diabetes

doi:10.3969/j.issn.2095-4344.1560

Abstract

Abstract:

BACKGROUND: Previous studies have shown that vascular endothelial dysfunction exists in patients with newly diagnosed type 2 diabetes. Alpha-lipoic acid is widely used as an antioxidant in patients with diabetic neuropathy. Can it improve the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetic patients? There is no such report.
OBJECTIVE: To investigate the impact of α-lipoic acid on circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus.
METHODS: Fifty newly diagnosed type 2 diabetes mellitus patients were randomly divided into control group (n=20) and alpha-lipoic acid group (n=30). Superoxide dismutase, glutathione peroxidase, malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol levels and number of endothelial progenitor cells were detected in the two groups before and 2 weeks after treatment. The differences and correlations between the two groups were analyzed.
RESULTS AND CONCLUSION: In the alpha-lipoic acid group, the number of endothelial progenitor cells, superoxide dismutase, glutathione peroxidase and high-density lipoprotein cholesterol levels were significantly increased after treatment compared with the baseline (P < 0.05), while the levels of malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly decreased after the treatment (P < 0.05). In the control group, the levels of triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly reduced after treatment compared with the baseline (P < 0.05), while the level of high-density lipoprotein cholesterol increased significantly after treatment (P < 0.05). Compared with the control group, the number of endothelial progenitor cells, superoxide dismutase and glutathione peroxidase levels were significantly increased in the alpha-lipoic acid group (P < 0.05), while the levels of malondialdehyde and 8-hydroxydeoxyguanosine were decreased in the alpha-lipoic acid group (P < 0.05). Multivariate linear regression analysis of the differences of the indexes before and after treatment in the alpha-lipoic acid group showed that the number of endothelial progenitor cells was correlated with the levels of glutathione peroxidase and malondialdehyde. To conclude, the treatment with α-lipoic acid increases the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus, which is associated with antioxidative stress.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Diabetes Mellitus, Type 2, Diabetic Angiopathies, Endothelial Cells, Thioctic Acid, Oxidative Stress, Tissue Engineering

CLC Number:

R453

Li Bopeng, Chen Shuchun, Tang Yong, Ren Luping. Alpha-lipoic acid increases circulating endothelial progenitor cells in newly diagnosed type 2 diabetes[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(5): 803-808.

Figures/Tables 6

References

[1] Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-841.

[2] Bo S, Ciccone G, Gancia R, et al. Mortality within the first 10 years of the disease in type 2 diabetic patients. Nutr Metab Cardiovasc Dis. 2006;16(1):8-12.

[3] Lombardo MF, Iacopino P, Cuzzola M, et al. Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood. Cytometry A. 2012;81(10):856-864.

[4] Russell JS, Brown JM. Circulating mouse Flk1+/c-Kit+/CD45- cells function as endothelial progenitors cells (EPCs) and stimulate the growth of human tumor xenografts. Mol Cancer. 2014;13:177.

[5] Pías-Peleteiro J, Campos F, Castillo J, et al.Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage.Neural Regen Res. 2017;12(4):558-561.

[6] Hamed S, Brenner B, Roguin A. Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res. 2011;91(1):9-15.

[7] 陈树春,宋光耀,孙阳,等. 初诊2型糖尿病患者外周血内皮祖细胞的研究[J]. 天津医药, 2010, 38(7): 549-551.

[8] 夏文华,饶玉霞. 2型糖尿病患者内皮祖细胞数量和功能研究[J]. 咸宁学院学报(医学版), 2012, 26(1): 12-14.

[9] Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999;85(3):221-228.

[10] Hristov M, Schmitz S, Nauwelaers F, et al. A flow cytometric protocol for enumeration of endothelial progenitor cells and monocyte subsets in human blood. J Immunol Methods. 2012;381(1-2):9-13.

[11] Ma XL, Sun XL, Wan CY, et al. Significance of circulating endothelial progenitor cells in patients with fracture healing process. J Orthop Res. 2012;30(11):1860-1866.

[12] Sen S, McDonald SP, Coates PT, et al. Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin Sci (Lond). 2011;120(7): 263-283.

[13] Zhou X, Patel D, Sen S, et al. Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis. J Vasc Surg. 2017;65(4):1161-1169.

[14] Lin CP, Lin FY, Huang PH, et al. Endothelial progenitor cell dysfunction in cardiovascular diseases: role of reactive oxygen species and inflammation. Biomed Res Int. 2013; 2013:845037.

[15] Barton M. Prevention and endothelial therapy of coronary artery disease. Curr Opin Pharmacol. 2013;13(2):226-241.

[16] Chen S, Sun L, Gao H, et al. Visfatin and oxidative stress influence endothelial progenitor cells in obese populations. Endocr Res. 2015;40(2):83-87.

[17] 陈树春,宋光耀,孙阳,等. 2型糖尿病一级亲属内皮祖细胞与氧化应激[J].中华内科杂志,2012,51(3):197-200.

[18] 陈树春,宋光耀.内皮祖细胞与氧化应激研究进展[J].中国组织工程研究与临床康复,2011,15(6): 1119-1122.

[19] Chen DD, Dong YG, Yuan H, et al. Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension. Hypertension. 2012;59(5):1037-1043.

[20] Kulikowska-Karpińska E, Czerw K. Estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration in the urine of cigarette smokers. Wiad Lek. 2015;68(1):32-38.

[21] Tabur S, Aksoy ?N, Korkmaz H, et al. Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma. Tumour Biol. 2015;36(4):2667-2674.

[22] Liu JT, Chen YL, Chen WC, et al. Role of pigment epithelium-derived factor in stem/progenitor cell-associated neovascularization. J Biomed Biotechnol. 2012;2012:871272.

[23] Zaragoza C, Gomez-Guerrero C, Martin-Ventura JL, et al. Animal models of cardiovascular diseases. J Biomed Biotechnol. 2011;2011:497841.

[24] Tousoulis D, Andreou I, Antoniades C, et al. Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization: therapeutic implications for cardiovascular diseases. Atherosclerosis. 2008;201(2): 236-247.

[25] Carracedo J, Merino A, Briceño C, et al. Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells. FASEB J. 2011;25(4):1314-1322.

[26] Pickering RJ, Rosado CJ, Sharma A, et al. Recent novel approaches to limit oxidative stress and inflammation in diabetic complications. Clin Transl Immunology. 2018;7(4): e1016.

[27] Sasaki S, Inoguchi T. The role of oxidative stress in the pathogenesis of diabetic vascular complications. Diabetes Metab J. 2012;36(4):255-261.

[28] Ceretta LB, Réus GZ, Abelaira HM, et al. Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. Exp Diabetes Res. 2012;2012: 302682.

[29] Hernández-Beltrán N, Moreno CB, Gutiérrez-Álvarez AM. Contribution of mitochondria to pain in diabetic neuropathy. Endocrinol Nutr. 2013;60(1):25-32.

[30] Rochette L, Ghibu S, Muresan A, et al. Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015;93(12):1021-1027.

[31] 陈树春,宋光耀,章冬梅,等. α-硫辛酸对高糖状态下内皮祖细胞的影响[J]. 细胞与分子免疫学杂志, 2012,28(3): 240-243.

[32] Zhao M, Chen JY, Chu YD, et al.Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials.Neural Regen Res. 2018; 13(6):1087-1095.

[33] 王景尚,孙明月,黄烨,等. α-硫辛酸对血糖波动状态下2型糖尿病大鼠血管内皮细胞功能及PI3K/Akt/GSK-3β通路的影响[J]. 中国全科医学, 2017,20(24): 2965-2971.