Oxidized low density lipoprotein, stem cells, and atherosclerosis

Lipids in Health and Disease

Sheng-hua Zhou¹  Ahmed Salah Salem Mohamed¹  Hui Yang¹ 

[1] Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

关键词: Oxidative stress;    LOX-1;    Atherosclerosis;    Stem cells;    Oxidized LDL;   

Others  :  1160259
DOI  :  10.1186/1476-511X-11-85

 received in 2012-05-10, accepted in 2012-06-16,  发布年份 2012

【 摘 要 】

Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms.

【 授权许可】

   
2012 Yang et al.;licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Kannel WB: New perspectives on cardiovascular risk factors. Am Heart J 1987, 114(1 Pt 2):213-219.
• [2]Law MR, Wald NJ, Thompson SG: By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994, 308(6925):367-372.
• [3]Mitra S, Goyal T, Mehta JL: Oxidized LDL, LOX-1 and Atherosclerosis. Cardiovasc Drugs Ther 2011, 25(5):419-429.
• [4]Imazu M, Ono K, Tadehara F, Kajiwara K, Yamamoto H, Sumii K, Tasaki N, Oiwa J, Shimohara Y, Gomyo Y, et al.: Plasma levels of oxidized low density lipoprotein are associated with stable angina pectoris and modalities of acute coronary syndrome. Int Heart J 2008, 49(5):515-524.
• [5]Itabe H, Ueda M: Measurement of plasma oxidized low-density lipoprotein and its clinical implications. J Atheroscler Thromb 2007, 14(1):1-11.
• [6]Fadini GP, Tjwa M: A role for TGF-beta in transforming endothelial progenitor cells into neointimal smooth muscle cells. Atherosclerosis 2010, 211(1):32-35.
• [7]Qian H, Yang Y, Li J, Huang J, Dou K, Yang G: The role of vascular stem cells in atherogenesis and post-angioplasty restenosis. Ageing Res Rev 2007, 6(2):109-127.
• [8]Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA: Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 2003, 108(4):457-463.
• [9]Xu Q, Zhang Z, Davison F, Hu Y: Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice. Circ Res 2003, 93(8):e76-e86.
• [10]Schenke-Layland K, Rhodes KE, Angelis E, Butylkova Y, Heydarkhan-Hagvall S, Gekas C, Zhang R, Goldhaber JI, Mikkola HK, Plath K, et al.: Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages. Stem Cells 2008, 26(6):1537-1546.
• [11]Adhikary S, Eilers M: Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005, 6(8):635-645.
• [12]Cole MD, Cowling VH: Transcription-independent functions of MYC: regulation of translation and DNA replication. Nat Rev Mol Cell Biol 2008, 9(10):810-815.
• [13]Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P: New type of POU domain in germ line-specific protein Oct-4. Nature 1990, 344(6265):435-439.
• [14]Pesce M, Scholer HR: Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 2001, 19(4):271-278.
• [15]Scholer HR: Octamania: the POU factors in murine development. Trends Genet 1991, 7(10):323-329.
• [16]Girouard SD, Laga AC, Mihm MC, Scolyer RA, Thompson JF, Zhan Q, Widlund HR, Lee CW, Murphy GF: SOX2 contributes to melanoma cell invasion. Lab Invest 2012, 92(3):362-370.
• [17]Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B: A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J Biol Chem 1996, 271(49):31384-31390.
• [18]Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284(5411):143-147.
• [19]Kashiwakura Y, Katoh Y, Tamayose K, Konishi H, Takaya N, Yuhara S, Yamada M, Sugimoto K, Daida H: Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22alpha promoter: in vitro differentiation of putative smooth muscle progenitor cells of bone marrow. Circulation 2003, 107(16):2078-2081.
• [20]Williams AR, Hare JM: Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 2011, 109(8):923-940.
• [21]Lasala GP, Minguell JJ: Vascular disease and stem cell therapies. Br Med Bull 2011, 98:187-197.
• [22]Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V: Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A 2007, 104(5):1643-1648.
• [23]Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL: A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 2003, 423(6938):409-414.
• [24]Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH: Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 2004, 10(1):55-63.
• [25]Boros P, Miller CM: Hepatocyte growth factor: a multifunctional cytokine. Lancet 1995, 345(8945):293-295.
• [26]Li Y, Yu J, Li M, Qu Z, Ruan Q: Mouse mesenchymal stem cells from bone marrow differentiate into smooth muscle cells by induction of plaque-derived smooth muscle cells. Life Sci 2011, 88(3–4):130-140.
• [27]Wu X, Huang L, Zhou Q, Song Y, Li A, Jin J, Cui B: Mesenchymal stem cells participating in ex vivo endothelium repair and its effect on vascular smooth muscle cells growth. Int J Cardiol 2005, 105(3):274-282.
• [28]Shin SH, Song HY, Kim MY, Do EK, Kim KH, Kim JH: Platelet-activating factor receptor mediates oxidized low density lipoprotein-induced migration of bone marrow-derived mesenchymal stem cells. Cell Physiol Biochem 2010, 26(4–5):689-698.
• [29]Yu J, Li Y, Li M, Qu Z, Ruan Q: Oxidized low density lipoprotein-induced transdifferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro. Int J Exp Pathol 2010, 91(1):24-33.
• [30]Carracedo J, Merino A, Briceno C, Soriano S, Buendia P, Calleros L, Rodriguez M, Martin-Malo A, Aljama P, Ramirez R: Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells. FASEB J 2011, 25(4):1314-1322.
• [31]Zoll J, Fontaine V, Gourdy P, Barateau V, Vilar J, Leroyer A, Lopes-Kam I, Mallat Z, Arnal JF, Henry P, et al.: Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition. Cardiovasc Res 2008, 77(3):471-480.
• [32]Rader DJ, Daugherty A: Translating molecular discoveries into new therapies for atherosclerosis. Nature 2008, 451(7181):904-913.
• [33]Steinberg D, Lewis A: Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation 1997, 95(4):1062-1071.
• [34]Ishigaki Y, Oka Y, Katagiri H: Circulating oxidized LDL: a biomarker and a pathogenic factor. Curr Opin Lipidol 2009, 20(5):363-369.
• [35]Yamashita H, Ehara S, Yoshiyama M, Naruko T, Haze K, Shirai N, Sugama Y, Ikura Y, Ohsawa M, Itabe H, et al.: Elevated plasma levels of oxidized low-density lipoprotein relate to the presence of angiographically detected complex and thrombotic coronary artery lesion morphology in patients with unstable angina. Circ J 2007, 71(5):681-687.
• [36]Salvayre R, Auge N, Benoist H, Negre-Salvayre A: Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta 2002, 1585(2–3):213-221.
• [37]Gruarin P, Thorne RF, Dorahy DJ, Burns GF, Sitia R, Alessio M: CD36 is a ditopic glycoprotein with the N-terminal domain implicated in intracellular transport. Biochem Biophys Res Commun 2000, 275(2):446-454.
• [38]Mehta JL, Li D: Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor. J Am Coll Cardiol 2002, 39(9):1429-1435.
• [39]Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, Yoshida H, Kawai C: Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci U S A 1987, 84(16):5928-5931.
• [40]Mitra S, Deshmukh A, Sachdeva R, Lu J, Mehta JL: Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy. Am J Med Sci 2011, 342(2):135-142.
• [41]Hagemann C, Anacker J, Ernestus RI, Vince GH: A complete compilation of matrix metalloproteinase expression in human malignant gliomas. World J Clin Oncol 2012, 3(5):67-79.
• [42]Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Takano T, et al.: Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001, 103(15):1955-1960.
• [43]Parthasarathy S, Santanam N: Mechanisms of oxidation, antioxidants, and atherosclerosis. Curr Opin Lipidol 1994, 5(5):371-375.
• [44]Hussain MM, Mahley RW, Boyles JK, Lindquist PA, Brecht WJ, Innerarity TL: Chylomicron metabolism. Chylomicron uptake by bone marrow in different animal species. J Biol Chem 1989, 264(30):17931-17938.
• [45]Hussain MM, Mahley RW, Boyles JK, Fainaru M, Brecht WJ, Lindquist PA: Chylomicron-chylomicron remnant clearance by liver and bone marrow in rabbits. Factors that modify tissue-specific uptake. J Biol Chem 1989, 264(16):9571-9582.
• [46]Negre-Salvayre A, Lopez M, Levade T, Pieraggi MT, Dousset N, Douste-Blazy L, Salvayre R: Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. II. Uptake and cytotoxicity of ultraviolet-treated LDL on lymphoid cell lines. Biochim Biophys Acta 1990, 1045(3):224-232.
• [47]Imanishi T, Hano T, Sawamura T, Nishio I: Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol 2004, 31(7):407-413.
• [48]Ma FX, Zhou B, Chen Z, Ren Q, Lu SH, Sawamura T, Han ZC: Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase. J Lipid Res 2006, 47(6):1227-1237.
• [49]Morawietz H: LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis. Dtsch Med Wochenschr 2010, 135(7):308-312.
• [50]Tang D, Lu J, Walterscheid JP, Chen HH, Engler DA, Sawamura T, Chang PY, Safi HJ, Yang CY, Chen CH: Electronegative LDL circulating in smokers impairs endothelial progenitor cell differentiation by inhibiting Akt phosphorylation via LOX-1. J Lipid Res 2008, 49(1):33-47.
• [51]Marathe GK, Prescott SM, Zimmerman GA, McIntyre TM: Oxidized LDL contains inflammatory PAF-like phospholipids. Trends Cardiovasc Med 2001, 11(3–4):139-142.
• [52]Beaudeux JL, Said T, Ninio E, Ganne F, Soria J, Delattre J, Soria C, Legrand A, Peynet J: Activation of PAF receptor by oxidised LDL in human monocytes stimulates chemokine releases but not urokinase-type plasminogen activator expression. Clin Chim Acta 2004, 344(1–2):163-171.
• [53]Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM: Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Crit Rev Clin Lab Sci 2003, 40(6):643-672.
• [54]Satomura K, Derubeis AR, Fedarko NS, Ibaraki-O'Connor K, Kuznetsov SA, Rowe DW, Young MF, Gehron Robey P: Receptor tyrosine kinase expression in human bone marrow stromal cells. J Cell Physiol 1998, 177(3):426-438.
• [55]Parhami F, Jackson SM, Tintut Y, Le V, Balucan JP, Territo M, Demer LL: Atherogenic diet and minimally oxidized low density lipoprotein inhibit osteogenic and promote adipogenic differentiation of marrow stromal cells. J Bone Miner Res 1999, 14(12):2067-2078.
• [56]Chu L, Hao H, Luo M, Huang Y, Chen Z, Lu T, Zhao X, Verfaillie CM, Zweier JL, Liu Z: Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation. J Cell Mol Med 2011, 15(2):423-432.
• [57]Lu T, Parthasarathy S, Hao H, Luo M, Ahmed S, Zhu J, Luo S, Kuppusamy P, Sen CK, Verfaillie CM, et al.: Reactive oxygen species mediate oxidized low-density lipoprotein-induced inhibition of oct-4 expression and endothelial differentiation of bone marrow stem cells. Antioxid Redox Signal 2010, 13(12):1845-1856.
• [58]Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, Nowicki PT, Messina LM: Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res 2010, 47(6):519-530.
• [59]Kuzkaya N, Weissmann N, Harrison DG, Dikalov S: Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J Biol Chem 2003, 278(25):22546-22554.
• [60]Chai J, Ji K, Lin J, Ye R, Tang J, Yang P: Effects of danshensu on function of EPCs which were damaged by Ox-LDL and study its possible mechanism. Zhongguo Zhong Yao Za Zhi 2009, 34(7):904-907.
• [61]Ji KT, Chai JD, Xing C, Nan JL, Yang PL, Tang JF: Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment. J Zhejiang Univ Sci B 2010, 11(8):618-626.
• [62]Huang PH, Tsai HY, Wang CH, Chen YH, Chen JS, Lin FY, Lin CP, Wu TC, Sata M, Chen JW, et al.: Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice–roles of endothelial progenitor cells and nitric oxide. Atherosclerosis 2010, 212(2):426-435.
• [63]Cheng J, Cui R, Chen CH, Du J: Oxidized low-density lipoprotein stimulates p53-dependent activation of proapoptotic Bax leading to apoptosis of differentiated endothelial progenitor cells. Endocrinology 2007, 148(5):2085-2094.
• [64]Ma FX, Ren Q, Han ZC: oxLDL reduced endothelial progenitor cells survival and function via regulating Akt/eNOS signal pathway. Zhonghua Xin Xue Guan Bing Za Zhi 2007, 35(2):173-177.
• [65]Imanishi T, Hano T, Matsuo Y, Nishio I: Oxidized low-density lipoprotein inhibits vascular endothelial growth factor-induced endothelial progenitor cell differentiation. Clin Exp Pharmacol Physiol 2003, 30(9):665-670.
• [66]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(6):1559-1568.
• [67]Krankel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K, Schuler G, Hambrecht R: Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol 2005, 25(4):698-703.
• [68]Ma FX, Han ZC: Akt signaling and its role in postnatal neovascularization. Histol Histopathol 2005, 20(1):275-281.
• [69]Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC: Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399(6736):597-601.
• [70]Franke TF, Kaplan DR, Cantley LC, Toker A: Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science 1997, 275(5300):665-668.
• [71]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.
• [72]Wu Y, Wang Q, Cheng L, Wang J, Lu G: Effect of oxidized low-density lipoprotein on survival and function of endothelial progenitor cell mediated by p38 signal pathway. J Cardiovasc Pharmacol 2009, 53(2):151-156.
• [73]Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S: The protein kinase complement of the human genome. Science 2002, 298(5600):1912-1934.
• [74]Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001, 22(2):153-183.
• [75]Di Santo S, Diehm N, Ortmann J, Volzmann J, Yang Z, Keo HH, Baumgartner I, Kalka C: Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5. Biochem Biophys Res Commun 2008, 373(4):528-532.
• [76]Shantsila E, Lip GY: Monocytes in acute coronary syndromes. Arterioscler Thromb Vasc Biol 2009, 29(10):1433-1438.
• [77]Swirski FK, Pittet MJ, Kircher MF, Aikawa E, Jaffer FA, Libby P, Weissleder R: Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease. Proc Natl Acad Sci U S A 2006, 103(27):10340-10345.
• [78]Porto ML, Lima LC, Pereira TM, Nogueira BV, Tonini CL, Campagnaro BP, Meyrelles SS, Vasquez EC: Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice. Lipids Health Dis 2011, 10:155. BioMed Central Full Text
• [79]Weber C, Zernecke A, Libby P: The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol 2008, 8(10):802-815.
• [80]Daub K, Seizer P, Stellos K, Kramer BF, Bigalke B, Schaller M, Fateh-Moghadam S, Gawaz M, Lindemann S: Oxidized LDL-activated platelets induce vascular inflammation. Semin Thromb Hemost 2010, 36(2):146-156.
• [81]Rohde E, Malischnik C, Thaler D, Maierhofer T, Linkesch W, Lanzer G, Guelly C, Strunk D: Blood monocytes mimic endothelial progenitor cells. Stem Cells 2006, 24(2):357-367.
• [82]Lambert JM, Lopez EF, Lindsey ML: Macrophage roles following myocardial infarction. Int J Cardiol 2008, 130(2):147-158.
• [83]Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, Mericskay M, Gierschik P, Biessen EA, Weber C: SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005, 96(7):784-791.
• [84]Zheng H, Fu G, Dai T, Huang H: Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol 2007, 50(3):274-280.
• [85]Daub K, Seizer P, Stellos K, Kramer BF, Bigalke B, Schaller M, Fateh-Moghadam S, Gawaz M, Lindemann S: Oxidized LDL-activated platelets induce vascular inflammation. Semin Thromb Hemost 2010, 36(2):146-156.
• [86]Hamed S, Brenner B, Abassi Z, Aharon A, Daoud D, Roguin A: Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus. Thromb Res 2010, 126(3):166-174.
• [87]Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A: Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J 2006, 27(18):2247-2255.
• [88]Maron DJ, Fazio S, Linton MF: Current perspectives on statins. Circulation 2000, 101(2):207-213.
• [89]Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM: HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001, 108(3):391-397.
• [90]Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T: HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells. J Clin Invest 2001, 108(3):399-405.
• [91]Hamed S, Brenner B, Aharon A, Daoud D, Roguin A: Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus. Cardiovasc Diabetol 2009, 8:56. BioMed Central Full Text
• [92]Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S: Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001, 103(24):2885-2890.
• [93]Shao H, Tan Y, Eton D, Yang Z, Uberti MG, Li S, Schulick A, Yu H: Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels. Stem Cells 2008, 26(5):1376-1384.
• [94]Ma FX, Chen F, Ren Q, Han ZC: Lovastatin restores the function of endothelial progenitor cells damaged by oxLDL. Acta Pharmacol Sin 2009, 30(5):545-552.
• [95]Lavi R, Zhu XY, Chade AR, Lin J, Lerman A, Lerman LO: Simvastatin decreases endothelial progenitor cell apoptosis in the kidney of hypertensive hypercholesterolemic pigs. Arterioscler Thromb Vasc Biol 2010, 30(5):976-983.