چاقی و آنژیوژنز

نوع مقاله : مقاله مروری

نویسنده

دانشجوی دکتری، کمیته ی تحقیقات دانشجویی، گروه فیزیولوژی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

امروزه شیوع بالای چاقی و عوارض آن در سراسر دنیا به یک معضل بهداشتی عمده تبدیل شده است. اضافه وزن خطر بیماری‌هایی مانند پرفشاری خون، بیماری‌های قلبی-عروقی، دیابت تیپ 2، انواع مشخص سرطان، سنگ‌های صفراوی و استئوآرتریت را افزایش می‌دهد. چاقی به صورت رشد بافت چربی سفید احشایی تعریف می‌شود و بافت چربی برای تأمین نیازهای متابولیک خود به طور متناسب نیاز به رشد رگ‌های خونی دارد که به صورت افزایش تعداد و یا اندازه‌ی رگ‌های خونی (آنژیوژنز/آرتریوزنز) صورت می‌گیرد. با توجه به ارتباط بسیار نزدیک آدیپوژنز و آنژیوژنز که در سالیان اخیر مورد توجه قرار گرفته است، مداخلات درمانی برای درمان چاقی با هدف قرار دادن عروق بافت چربی آینده‌ی نویدبخشی را ترسیم می‌کند. در این مقاله‌ی مروری، به بافت چربی، نقش و عملکرد مهم عروق در بافت چربی و ارتباط چاقی و آنژیوژنز پرداخته شده است و در انتها در مورد استفاده از مواد آنتی‌آنژیوژنز برای درمان چاقی به عنوان یک رویکرد جدید مطالبی ارائه شده است.

کلیدواژه‌ها

عنوان مقاله [English]

Obesity and Angiogenesis

نویسنده [English]

  • Zoya Tahergurabi
PhD Student, Student Research Committee, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Nowadays, high prevalence of obesity and its consequences is considered as a major health complication worldwide. Overweight increases risk of diseases such as hypertension, cardiovascular diseases, type 2 diabetes, certain types of cancer, gallstone, and osteoarthritis. Obesity is defined as growth of visceral white adipose tissue. On the other hand, in order to supply for metabolic needs of adipose tissue, depends on appropriate growth of blood vessels, either in number and/or in size (angiogenesis/arteriogenesis). Moreover, the very close interconnection between adipogenesis and angiogenesis has been considered in recent years. Therapeutic interventions for treating obesity by targeting vessels of adipose tissue illustrate a promising future. In this review, we discussed adipose tissue, important roles and functions of vessels in adipose tissue, obesity, and angiogenesis. We finally presented suggestions on how to use anti-angiogenesis agents for treatment of obesity as a novel approach.

کلیدواژه‌ها [English]

  • Obesity
  • Angiogenesis
  • Adipogenesis

مراجع

  1. Kopelman PG. Obesity as a medical problem. Nature 2000; 404(6778): 635-43.
  2. Prentice AM. The emerging epidemic of obesity in developing countries. Int J Epidemiol 2006; 35(1): 93-9.
  3. World Health Organisation. Global Database on Body Mass Index [Online]. 2008; Available from: URL:http://apps.who.int/bmi/index.jsp/.
  4. Daquinag AC, Zhang Y, Kolonin MG. Vascular targeting of adipose tissue as an anti-obesity approach. Trends Pharmacol Sci 2011; 32(5): 300-7.
  5. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature 2008; 453(7196): 783-7.
  6. The burden of overweight and obesity in the Asia-Pacific region. Obes Rev 2007; 8(3): 191-6.
  7. Lawlor DA, Chaturvedi N. Treatment and prevention of obesity--are there critical periods for intervention? Int J Epidemiol 2006; 35(1): 3-9.
  8. Low S, Chin MC, Deurenberg-Yap M. Review on epidemic of obesity. Ann Acad Med Singapore 2009; 38(1): 57-9.
  9. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L. Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis. Ann Intern Med 2003; 138(1): 24-32.
  10. Rashidi A, Mohammadpour-Ahranjani B, Vafa MR, Karandish M. Prevalence of obesity in Iran. Obes Rev 2005; 6(3): 191-2.
  11. Hausman GJ, Richardson RL. Adipose tissue angiogenesis. J Anim Sci 2004; 82(3): 925-34.
  12. Cho CH, Koh YJ, Han J, Sung HK, Jong LH, Morisada T, et al. Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ Res 2007; 100(4): e47-e57.
  13. Lijnen HR. Angiogenesis and obesity. Cardiovasc Res 2008; 78(2): 286-93.
  14. Intengan HD, Schiffrin EL. Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 2000; 36(3): 312-8.
  15. Seifalian AM, Filippatos TD, Joshi J, Mikhailidis DP. Obesity and arterial compliance alterations. Curr Vasc Pharmacol 2010; 8(2): 155-68.
  16. Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R, et al. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 2004; 109(5): 656-63.
  17. Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci U S A 2001; 98(11): 6390-5.
  18. Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol 2007; 2: 31-56.
  19. Filippatos TD, Derdemezis CS, Gazi IF, Lagos K, Kiortsis DN, Tselepis AD, et al. Increased plasma visfatin levels in subjects with the metabolic syndrome. Eur J Clin Invest 2008; 38(1): 71-2.
  20. Nguyen QM, Srinivasan SR, Xu JH, Chen W, Berenson GS. Racial (black-white) divergence in the association between adiponectin and arterial stiffness in asymptomatic young adults: the Bogalusa heart study. Am J Hypertens 2008; 21(5): 553-7.
  21. Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 2006; 290(2): H560-H576.
  22. Gummersbach C, Hemmrich K, Kroncke KD, Suschek CV, Fehsel K, Pallua N. New aspects of adipogenesis: radicals and oxidative stress. Differentiation 2009; 77(2): 115-20.
  23. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 2004; 110(3): 349-55.
  24. Ntambi JM, Young-CheulKim K. Adipocyte Differentiation and Gene Expression. J Nutr 2000; 130(12): 3122S-6S.
  25. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006; 2(1): 35-43.
  26. Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell 2008; 135(2): 240-9.
  27. Tang QQ, Otto TC, Lane MD. Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. PNAS 2004; 101(26): 9607-11.
  28. Fajas L. Adipogenesis: a cross-talk between cell proliferation and cell differentiation. Ann Med 2003; 35(2): 79-85.
  29. Yun Z, Maecker HL, Johnson RS, Giaccia AJ. Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell 2002; 2(3): 331-41.
  30. Wada T, Shimba S, Tezuka M. Transcriptional regulation of the hypoxia inducible factor-2alpha (HIF-2alpha) gene during adipose differentiation in 3T3-L1 cells. Biol Pharm Bull 2006; 29(1): 49-54.
  31. Shimba S, Wada T, Hara S, Tezuka M. EPAS1 promotes adipose differentiation in 3T3-L1 cells. Journal of Biological Chemistry 2004; 279(39): 40946-53.
  32. Hiromori Y, Nishikawa J, Yoshida I, Nagase H, Nakanishi T. Structure-dependent activation of peroxisome proliferator-activated receptor (PPAR) gamma by organotin compounds. Chem Biol Interact 2009; 180(2): 238-44.
  33. Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, et al. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2 . Genes & Dev 2003; 17: 1352-65.
  34. Xu J, Liao K. Protein kinase B/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation. J Biol Chem 2004; 279(34): 35914-22.
  35. Zarei M, Khazaei M, Sharifi MR, Pourshanazari AA. Coronary angiogenesis during experimental hypertension: is it reversible? J Res Med Sci 2011; 16(3): 269-75.
  36. Khazaei M, Fallahzadeh AR, Sharifi MR, Afsharmoghaddam N, HaghjooyJavanmard SH, Salehi E. Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats. Clinics (Sao Paulo) 2011; 66(8): 1419-24.
  37. Amjadi F, Javanmard SH, Zarkesh-Esfahani H, Khazaei M, Narimani M. Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production. J Exp Clin Cancer Res 2011; 30: 21.
  38. Auerbach R, Lewis R, Shinners B, Kubai L, Akhtar N. Angiogenesis assays: a critical overview. Clin Chem 2003; 49(1): 32-40.
  39. Sainson RC, Aoto J, Nakatsu MN, Holderfield M, Conn E, Koller E, et al. Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J 2005; 19(8): 1027-9.
  40. Radtke F, Schweisguth F, Pear W. The Notch 'gospel'. EMBO Rep 2005; 6(12): 1120-5.
  41. Liu ZJ, Shirakawa T, Li Y, Soma A, Oka M, Dotto GP, et al. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol 2003; 23(1): 14-25.
  42. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. JCB 2012; 161(6): 1163-77.
  43. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9(6): 685-93.
  44. Cleaver O, Melton DA. Endothelial signaling during development. Nat Med 2003; 9(6): 661-8.
  45. Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 2005; 15(1): 102-11.
  46. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307(5706): 58-62.
  47. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000; 6(4): 389-95.
  48. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 2004; 5(1): 74-80.
  49. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 2001; 7(2): 186-91.
  50. Ledoux S, Queguiner I, Msika S, Calderari S, Rufat P, Gasc JM, et al. Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity. Diabetes 2008; 57(12): 3247-57.
  51. Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K, et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 2001; 28(2): 131-8.
  52. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De MM, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 2001; 7(5): 575-83.
  53. Voros G, Maquoi E, Demeulemeester D, Clerx N, Collen D, Lijnen HR. Modulation of angiogenesis during adipose tissue development in murine models of obesity. Endocrinology 2005; 146(10): 4545-54.
  54. Christiaens V, Lijnen HR. Angiogenesis and development of adipose tissue. Mol Cell Endocrinol 2010; 318(1-2): 2-9.
  55. Saiki A, Watanabe F, Murano T, Miyashita Y, Shirai K. Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro. Int J Obes (Lond ) 2006; 30(11): 1676-84.
  56. Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 2000; 7(3): 165-97.
  57. Tartare-Deckert S, Chavey C, Monthouel MN, Gautier N, Van OE. The matricellular protein SPARC/osteonectin as a newly identified factor up-regulated in obesity. J Biol Chem 2001; 276(25): 22231-7.
  58. Bradshaw AD, Graves DC, Motamed K, Sage EH. SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc Natl Acad Sci U S A 2003; 100(10): 6045-50.
  59. Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 2003; 47(3): 149-61.
  60. Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 6(4): 460-3.
  61. Carlson TR, Feng Y, Maisonpierre PC, Mrksich M, Morla AO. Direct cell adhesion to the angiopoietins mediated by integrins. J Biol Chem 2001; 276(28): 26516-25.
  62. Morange PE, Bastelica D, Bonzi MF, Van HB, Collen D, Juhan-Vague I, et al. Influence of t-pA and u-PA on adipose tissue development in a murine model of diet-induced obesity. Thromb Haemost 2002; 87(2): 306-10.
  63. Neels JG, Thinnes T, Loskutoff DJ. Angiogenesis in an in vivo model of adipose tissue development. FASEB J 2004; 18(9): 983-5.
  64. Suganami E, Takagi H, Ohashi H, Suzuma K, Suzuma I, Oh H, et al. Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells. Diabetes 2004; 53(9): 2443-8.
  65. Matsuzawa Y. Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 2006; 3(1): 35-42.
  66. Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A 2004; 101(8): 2476-81.
  67. Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res 2004; 94(4): e27-e31.
  68. Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med 2000; 6(1): 41-8.
  69. Agah A, Kyriakides TR, Lawler J, Bornstein P. The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice. Am J Pathol 2002; 161(3): 831-9.
  70. Alvarez-Llamas G, Szalowska E, de Vries MP, Weening D, Landman K, Hoek A, et al. Characterization of the human visceral adipose tissue secretome. Mol Cell Proteomics 2007; 6(4): 589-600.
  71. Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest 2007; 117(9): 2362-8.
  72. Camp HS, Ren D, Leff T. Adipogenesis and fat-cell function in obesity and diabetes. Trends Mol Med 2002; 8(9): 442-7.
  73. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006; 6(11): 835-45.
  74. Shaked Y, Shaked A, Franco M, Lee CR, Man SH, Cheung AM, et al. Therapy-Induced Acute Recruitment of Circulating Endothelial Progenitor Cells to Tumors. Science 2006; 313(5794): 1785-7.
  75. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004; 95(1): 9-20.
  76. Cao Y. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov 2010; 9(2): 107-15.
  77. Meliga E, Strem BM, Duckers HJ, Serruys PW. Adipose-derived cells. Cell Transplant 2007; 16(9): 963-70.
  78. Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 2007; 28(21): 2667-77.
  79. Grenier G, Scime A, Le GF, Asakura A, Perez-Iratxeta C, Andrade-Navarro MA, et al. Resident endothelial precursors in muscle, adipose, and dermis contribute to postnatal vasculogenesis. Stem Cells 2007; 25(12): 3101-10.
  80. Rutkowski JM, Davis KE, Scherer PE. Mechanisms of obesity and related pathologies: the macro- and microcirculation of adipose tissue. FEBS J 2009; 276(20): 5738-46.
  81. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, et al. White fat progenitor cells reside in the adipose vasculature. Science 2008; 322(5901): 583-6.
  82. Powell K. Obesity: the two faces of fat. Nature 2007; 447(7144): 525-7.
  83. Jansson PA. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007; 262(2): 173-83.
  84. Bakker W, Eringa EC, Sipkema P, van Hinsbergh VW. Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity. Cell Tissue Res 2009; 335(1): 165-89.
  85. Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab 2009; 94(9): 3171-82.
  86. Baillargeon J, Rose DP. Obesity, adipokines, and prostate cancer (review). Int J Oncol 2006; 28(3): 737-45.
  87. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005; 115(5): 1111-9.
  88. Mu H, Ohashi R, Yan S, Chai H, Yang H, Lin P, et al. Adipokine resistin promotes in vitro angiogenesis of human endothelial cells. Cardiovasc Res 2006; 70(1): 146-57.
  89. Saiki A, Watanabe F, Murano T, Miyashita Y, Shirai K. Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro. Int J Obes (Lond ) 2006; 30(11): 1676-84.
  90. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002; 8(7): 731-7.
  91. Eriksson A, Cao R, Pawliuk R, Berg SM, Tsang M, Zhou D, et al. Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PlGF-1/VEGF heterodimers. Cancer Cell 2002; 1(1): 99-108.
  92. Bouloumie A, Lolmede K, Sengenes C, Galitzky J, Lafontan M. Angiogenesis in adipose tissue. Ann Endocrinol (Paris ) 2002; 63(2 Pt 1): 91-5.
  93. Crandall DL, Busler DE, McHendry-Rinde B, Groeling TM, Kral JG. Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1. J Clin Endocrinol Metab 2000; 85(7): 2609-14.
  94. Kubo Y, Kaidzu S, Nakajima I, Takenouchi K, Nakamura F. Organization of extracellular matrix components during differentiation of adipocytes in long-term culture. In Vitro Cell Dev Biol Anim 2000; 36(1): 38-44.
  95. Bouloumie A, Sengenes C, Portolan G, Galitzky J, Lafontan M. Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 2001; 50(9): 2080-6.
  96. Maquoi E, Demeulemeester D, Voros G, Collen D, Lijnen HR. Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation. Thromb Haemost 2003; 89(4): 696-704.
  97. Lijnen HR, Demeulemeester D, Van HB, Collen D, Maquoi E. Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice. Thromb Haemost 2003; 89(2): 249-55.
  98. Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, et al. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 2009; 29(16): 4467-83.
  99. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56(4): 901-11.
  100. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond) 2008; 32(3): 451-63.
  101. Lazar MA. How obesity causes diabetes: not a tall tale. Science 2005; 307(5708): 373-5.
  102. Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, et al. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci U S A 2002; 99(16): 10730-5.
  103. Fukumura D, Ushiyama A, Duda DG, Xu L, Tam J, Krishna V, et al. Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis. Circ Res 2003; 93(9): e88-e97.
  104. Lijnen HR, Christiaens V, Scroyen I, Voros G, Tjwa M, Carmeliet P, et al. Impaired adipose tissue development in mice with inactivation of placental growth factor function. Diabetes 2006; 55(10): 2698-704.
  105. Steinbrook R. The price of sight--ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med 2006; 355(14): 1409-12.
مجله دانشکده پزشکی اصفهان
دوره 29، شماره 172 - شماره پیاپی 172
بهمن و اسفند 1390
صفحه 2899-2914

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  • تاریخ دریافت: 09 بهمن 1390
  • تاریخ بازنگری: 30 فروردین 1403
  • تاریخ پذیرش: 17 فروردین 1401

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