Browse > Article
http://dx.doi.org/10.4162/nrp.2014.8.4.368

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose  

Zeng, Yao-Chi (Department of Clinical Nutrition, Shenzhen Traditional Chinese Medicine Hospital)
Mu, Gui-Ping (Department of Central Laboratory, Shenzhen Traditional Chinese Medicine Hospital)
Huang, Shu-Fen (Department of Health Education, Shenzhen Traditional Chinese Medicine Hospital)
Zeng, Xue-Hui (Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital)
Cheng, Hong (Department of Cardiovascular Medicine, Shenzhen Traditional Chinese Medicine Hospital)
Li, Zhong-Xin (Association of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital)
Publication Information
Nutrition Research and Practice / v.8, no.4, 2014 , pp. 368-376 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and $50{\mu}g/mL$ of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and $50{\mu}g/mL$ of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.
Keywords
Lycopene; high glucose; endothelial progenitor cells; p38 MAPK; curve fitting;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Almdal T, Scharling H, Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med 2004;164:1422-6.   DOI   ScienceOn
2 Avogaro A, Fadini GP, Gallo A, Pagnin E, de Kreutzenberg S. Endothelial dysfunction in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2006;16 Suppl 1:S39-45.   DOI   ScienceOn
3 Cubbon RM, Kahn MB, Wheatcroft SB. Effects of insulin resistance on endothelial progenitor cells and vascular repair. Clin Sci (Lond) 2009;117:173-90.   DOI   ScienceOn
4 Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 2003;107:461-8.   DOI   ScienceOn
5 Fadini GP, Avogaro A. Potential manipulation of endothelial progenitor cells in diabetes and its complications. Diabetes Obes Metab 2010;12:570-83.   DOI   ScienceOn
6 Reinhard H, Jacobsen PK, Lajer M, Pedersen N, Billestrup N, Mandrup-Poulsen T, Parving HH, Rossing P. Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes. Diabetologia 2010;53:2129-33.   DOI   ScienceOn
7 Liao YF, Chen LL, Zeng TS, Li YM, Fan Y, Hu LJ, Ling Y. Number of circulating endothelial progenitor cells as a marker of vascular endothelial function for type 2 diabetes. Vasc Med 2010;15:279-85.   DOI   ScienceOn
8 Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. Blood- derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest 2000;106:571-8.   DOI   ScienceOn
9 Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 2005;115: 572-83.   DOI
10 Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593-600.   DOI   ScienceOn
11 Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005;45:1449-57.   DOI   ScienceOn
12 Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, de Boer HC, Verhaar MC, Braam B, Rabelink TJ, van Zonneveld AJ. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004;53:195-9.   DOI   ScienceOn
13 Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Circulation 2003;108:1527-32.   DOI   ScienceOn
14 Chen YH, Lin SJ, Lin FY, Wu TC, Tsao CR, Huang PH, Liu PL, Chen YL, Chen JW. High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes 2007;56:1559-68.   DOI   ScienceOn
15 Sheu ML, Ho FM, Yang RS, Chao KF, Lin WW, Lin-Shiau SY, Liu SH. High glucose induces human endothelial cell apoptosis through a phosphoinositide 3-kinase-regulated cyclooxygenase-2 pathway. Arterioscler Thromb Vasc Biol 2005;25:539-45.   DOI   ScienceOn
16 Yoshizumi M, Abe J, Tsuchiya K, Berk BC, Tamaki T. Stress and vascular responses: atheroprotective effect of laminar fluid shear stress in endothelial cells: possible role of mitogen-activated protein kinases. J Pharmacol Sci 2003;91:172-6.   DOI   ScienceOn
17 Uruno A, Sugawara A, Kudo M, Satoh F, Saito A, Ito S. Stimulatory effects of low-dose 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor fluvastatin on hepatocyte growth factor-induced angiogenesis: involvement of p38 mitogen-activated protein kinase. Hypertens Res 2008;31:2085-96.   DOI   ScienceOn
18 McGinn S, Saad S, Poronnik P, Pollock CA. High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase. Am J Physiol Endocrinol Metab 2003;285:E708-17.   DOI   ScienceOn
19 Wang H, Wang L, Li KZ, Ling R, Sun BH, Ma FC, Li XJ. Culture and identification of endothelial progenitor cells from human peripheral blood. Chin J Clin Rehabil 2006;10:47-9.
20 Azuma K, Kawamori R, Toyofuku Y, Kitahara Y, Sato F, Shimizu T, Miura K, Mine T, Tanaka Y, Mitsumata M, Watada H. Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol 2006;26:2275-80.   DOI   ScienceOn
21 Wang HX, Zhao S, Li BG, Mao H, Shao SY. Effects of high-glucose on proliferation and apoptosis in endothelial progenitor cells of type 2 diabetes mellitus. Chin J Pathophysiol 2007;23:2210-3.
22 Kuwana M, Okazaki Y, Kodama H, Satoh T, Kawakami Y, Ikeda Y. Endothelial differentiation potential of human monocyte-derived multipotential cells. Stem Cells 2006;24:2733-43.   DOI   ScienceOn
23 Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002;106:2781-6.   DOI   ScienceOn
24 Nakamura N, Naruse K, Kobayashi Y, Matsuki T, Hamada Y, Nakashima E, Kamiya H, Hata M, Nishikawa T, Enomoto A, Takahashi M, Murohara T, Matsubara T , Oiso Y, Nakamura J. High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt. J Diabetes Investig 2011;2:262-70.   DOI
25 Gianetti J, Pedrinelli R, Petrucci R, Lazzerini G, De Caterina M, Bellomo G, De Caterina R. Inverse association between carotid intima-media thickness and the antioxidant lycopene in atherosclerosis. Am Heart J 2002;143:467-74.   DOI   ScienceOn
26 Rissanen T, Voutilainen S, Nyyssonen K, Salonen JT. Lycopene, atherosclerosis, and coronary heart disease. Exp Biol Med (Maywood) 2002;227:900-7.
27 Rissanen TH, Voutilainen S, Nyyssonen K, Salonen R, Kaplan GA, Salonen JT. Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr 2003;77:133-8.
28 Adams RH, Porras A, Alonso G, Jones M, Vintersten K, Panelli S, Valladares A, Perez L, Klein R, Nebreda AR. Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development. Mol Cell 2000;6:109-16.   DOI   ScienceOn
29 Kuki S, Imanishi T, Kobayashi K, Matsuo Y, Obana M, Akasaka T. Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J 2006;70:1076-81.   DOI   ScienceOn
30 Seeger FH, Haendeler J, Walter DH, Rochwalsky U, Reinhold J, Urbich C, Rossig L, Corbaz A, Chvatchko Y, Zeiher AM, Dimmeler S. p38 mitogen-activated protein kinase downregulates endothelial progenitor cells. Circulation 2005;111:1184-91.   DOI   ScienceOn
31 Kim GY, Kim JH, Ahn SC, Lee HJ, Moon DO, Lee CM, Park YM. Lycopene suppresses the lipopolysaccharide-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and nuclear factor- kappaB. Immunology 2004;113:203-11.   DOI   ScienceOn
32 Di Mascio P, Kaiser S, Sies H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys 1989;274:532-8.   DOI   ScienceOn
33 Sesso HD, Buring JE, Norkus EP, Gaziano JM. Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Am J Clin Nutr 2004;79:47-53.
34 Martin KR, Wu D, Meydani M. The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells. Atherosclerosis 2000; 150:265-74.   DOI   ScienceOn
35 Chan CM, Fang JY, Lin HH, Yang CY, Hung CF. Lycopene inhibits PDGF-BB-induced retinal pigment epithelial cell migration by suppression of PI3K/Akt and MAPK pathways. Biochem Biophys Res Commun 2009;388:172-6.   DOI   ScienceOn
36 Van Craenenbroeck EM, Conraads VM. Endothelial progenitor cells in vascular health: focus on lifestyle. Microvasc Res 2010;79:184-92.   DOI   ScienceOn
37 Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol 2004;24:1442-7.   DOI   ScienceOn
38 Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 2001;88:167-74.   DOI   ScienceOn
39 Lin CY, Huang CS, Hu ML. The use of fetal bovine serum as delivery vehicle to improve the uptake and stability of lycopene in cell culture studies. Br J Nutr 2007;98:226-32.   DOI   ScienceOn
40 Vaishampayan U, Hussain M, Banerjee M, Seren S, Sarkar FH, Fontana J, Forman JD, Cher ML, Powell I, Pontes JE, Kucuk O. Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer 2007;59:1-7.   DOI   ScienceOn
41 Ylonen K, Alfthan G, Groop L, Saloranta C, Aro A, Virtanen SM. Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study. Am J Clin Nutr 2003;77:1434-41.
42 Liu X, Qu D, He F, Lu Q, Wang J, Cai D. Effect of lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats. Asia Pac J Clin Nutr 2007;16 Suppl 1:244-8.
43 Balestrieri ML, De Prisco R, Nicolaus B, Pari P, Moriello VS, Strazzullo G, Iorio EL, Servillo L, Balestrieri C. Lycopene in association with alpha-tocopherol or tomato lipophilic extracts enhances acyl- platelet-activating factor biosynthesis in endothelial cells during oxidative stress. Free Radic Biol Med 2004;36:1058-67.   DOI   ScienceOn
44 Suganuma H, Inakuma T. Protective effect of dietary tomato against endothelial dysfunction in hypercholesterolemic mice. Biosci Biotechnol Biochem 1999;63:78-82.   DOI   ScienceOn
45 Lowe GM, Booth LA, Young AJ, Bilton RF. Lycopene and beta- carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses. Free Radic Res 1999;30:141-51.   DOI   ScienceOn
46 Yeh S, Hu M. Antioxidant and pro-oxidant effects of lycopene in comparison with beta-carotene on oxidant-induced damage in Hs68 cells. J Nutr Biochem 2000;11:548-54.   DOI   ScienceOn
47 Piconi L, Quagliaro L, Assaloni R, Da Ros R, Maier A, Zuodar G, Ceriello A. Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction. Diabetes Metab Res Rev 2006;22:198-203.   DOI   ScienceOn
48 Tamareille S, Mignen O, Capiod T, Rücker-Martin C, Feuvray D. High glucose-induced apoptosis through store-operated calcium entry and calcineurin in human umbilical vein endothelial cells. Cell Calcium 2006;39:47-55.   DOI   ScienceOn