• Home
  • An Overview of Angiogenesis and Chemical and Physiological Angiogenic Factors: Short Review

Share To

Article Url


Manuscript ID : JCHR-2106-1326 (R3) Visit : 346 Page: 411 - 422

10.22034/jchr.2022.1932834.1326

Article Type: Original Research

An Overview of Angiogenesis and Chemical and Physiological Angiogenic Factors: Short Review

Subject Areas : Journal of Chemical Health Risks

Mehrnoosh Sedighi 1 , Mehrdad Namdari 2 , Payam Mahmoudi 3 , Afshin Khani 4 , Aliasghar Manouchehri 5 , Milad Anvari 6

1 - Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
2 - Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khoramabad, Iran
3 - Cardiovascular Research Center, Mazandran Heart Center, Sari, Iran
4 - Cardiovascular Research Center, Mazandran Heart Center, Sari, Iran
5 - Assistant Professor, Department of Internal Medicine, Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Iran
6 - Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran

Received: 2021-06-12 Accepted : 2022-01-04 Published : 2023-09-01

Keywords: angiogenesis, HEART, VEGF, Angiogenic factors, TGF,

Abstract :

Angiogenesis refers to the formation of new blood vessels from existing ones, which can occur in both physiologic and pathologic conditions. Lack of tissue oxygen is the main stimulator of angiogenesis accompanied by increasing in HIF-1α-(hypoxia-inducible factor-1α) expression as a nuclear transcription factor. Other factors such as VEGF (vascular endothelial growth factor), FGF2 (fibroblast growth factor2), and TGF (transforming growth factor) are involved in angiogenesis, too. To control diabetes and tumoral disease, abnormal angiogenesis inhibition can be useful besides stimulation that can be helpful in cardiovascular disease. In this study, we have reviewed the mechanisms and stimulators of angiogenesis and its influential factors. The most important angiogenic factors are MMP, Ang, FGF, and VEGF. Ang is not directly involved in the process of angiogenesis but sometimes destabilize the arteries. In contrast to angiostatin, endostatin TIMP and TSP1 act as the most important angiostatic factors. Many attempts have been made to identify the mechanisms and factors involved in this process but angiogenic inhibitors that inhibit the growth of cancerous masses or tumors in the body have not yet been adequately investigated

References:


  1. 1. Carmeliet P., 2015. Angiogenesis in health and disease. Nature medicine. 9(6), 653-60.
    2.
  2. Yadav L., Puri N., Rastogi V., Satpute P., Sharma V. 2015. Tumour angiogenesis and angiogenic inhibitors: a review. Journal of clinical and diagnostic research: J Clin Diagn Res. 9(6), E01–E05.
    3.
  3. Huang D., Lan H., Liu F., Wang S., Chen X., Jin K., 2015., Anti-angiogenesis or pro-angiogenesis for cancer treatment: focus on drug distribution. International Journal of Clinical and Experimental Medicine. 8(6), 8369–8376
    4.
  4. Auerbach R., Lewis R., Shinners B., Kubai L., Akhtar N., 2003,. Angiogenesis assays: a critical overview. Clinical Chemistry. 49(1), 32-40.
    5.
  5. Radtke F., Schweisguth F., Pear W., 2005., The Notch ‘gospel’ Workshop on Notch Signalling in Development and Cancer. EMBO Reports. 6(12), 1120-1125.
    6.
  6. Liu Z.J., Shirakawa T., Li Y., Soma A., Oka M., Dotto G.P., 2003. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Molecular and Cellular Biology. 23(1), 14-25.
    7.
  7. Suhr F., Rosenwick C., Vassiliadis A., Bloch W., Brixius K., 2010., Regulation of extracellular matrix compounds involved in angiogenic processes in short‐and long‐track
    8.

 

 

 

elite runners. Scandinavian Journal of Medicine & Science in Sports. 20(3), 441-8.

  1. Jing S.W., Wang Y.D., Kuroda M., Su J.W., Sun G.G., Liu Q., 2012., HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inhibiting E-cadherin and promoting MMP-2 expression. Acta Medica Okayama. 66(5), 399-407.
    2.
  2. Friedmann B., Frese F., Menold E., Bärtsch P., 2007. Effects of acute moderate hypoxia on anaerobic capacity in endurance-trained runners. European Journal of Applied Physiology. 101(1), 67-73.
    3.
  3. Faramarzi M., Nuri R., 2017. The effects of ten weeks resistance training on resting levels of some angiogenesis factors among men with prostate cancer. Yafteh. 19(4), 129-139.
    4.
  4. Yang G., Nowsheen S., Aziz K., Georgakilas A.G. 2013., Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs. Pharmacology & Therapeutics. 139(3), 392-404.
    5.
  5. Simon M.P., Tournaire R., Pouyssegur J., 2008. The angiopoietin‐2 gene of endothelial cells is up‐regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA‐2 and Ets‐1. Journal of Cellular Physiology. 217(3), 809-18.
    6.
  6. Liu D.H., Zhang X.Y., Fan D.M., Huang Y.X., Zhang J.S., Huang W.Q., 2001. Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma. World J Gastroenterol. 7(4), 500–505.
    7.
  7. Zachary I., Gliki G., 2001. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovascular Research. 49(3), 568-581.
    8.
  8. Mimori K., Fukagawa T., Kosaka Y., Kita Y., Ishikawa K., Etoh T., 2008 . Hematogenous metastasis in gastric cancer requires isolated tumor cells and expression of vascular endothelial growth factor receptor-1. Clin Cancer Res. 14(9), 2609–2616.
    9.
  9. Hsu J.Y.C., McKeon R, Goussev S., Werb Z., Lee J.U., Trivedi A., 2006. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. Journal of Neuroscience. 26(39), 9841-9850.
    10.
  10. Lee H.H, Son Y.J., Lee W.H., Park Y.W., Chae S.W., Cho W.J., 2010. Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer. Int J Cancer. 126(8),1817–1827.
    11.
  11. Masson V., De La Ballina LR., Munaut C., Wielockx B., Jost M., Maillard C., 2005.Contribution of host MMP‐2 and MMP‐9 to promote tumor vascularization and invasion of malignant keratinocytes. The FASEB Journal. 19(2), 1-17.
    12.
  12. Lambert V., Wielockx B., Munaut C., Galopin C., Jost M., Itoh T., 2003. MMP‐2 and MMP‐9 synergize in promoting choroidal neovascularization. The FASEB Journal. 17(15), 2290-2292.
    13.
  13. Bente P., 2011. Exercise includes myokines and their role in choronic disease. Brain Behav Immun. 25(2), 811-816.
    14.
  14. Christiaens V., Lijnen H., 2010. Angiogenesis and development of adipose tissue. Molecular and Cellular Endocrinology. 318(1-2), 2-9.
    15.
  15. Gustafsson T., Kraus WE., 2001. Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology. Front Biosci. 6, 75-89.
    16.
  16. Smith P.J., Spurrell E.L., Coakley J., Hinds C.J., Ross R.J., Krainer A.R., Chew S.L., 2002. An exonic splicing enhancer in human IGF-I pre-mRNA mediates recognition of alternative exon 5 by the serine-arginine protein splicing factor-2/alternative splicing factor. Endocrinology.143(13),146–154.
    17.
  17. David C.J., Manley J.L., 2010. Alternative pre-mRNA splicing regulation in cancer: Pathways and programs unhinged. Genes Dev. 24(21), 2343–2364.
    18.
  18. Ranjbar K., Rahmani-Nia F., Shahabpour E., 2016. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction. Journal of Physiology and Biochemistry. 72(3), 393-404.
    19.
  19. Cao R., Brakenhielm E., Wahlestedt C., Thyberg J., Cao Y., 2001., Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proceedings of the National Academy of Sciences. 98(11), 6390-6395.
    20.
  20. Powers C., McLeskey S., Wellstein A., 2000. Fibroblast growth factors, their receptors and signaling. Endocrine-Related Cancer. 7(3), 165-197.
    21.
  21. Langston W., Chidlow J.H., Booth B.A., Barlow SC., Lefer DJ., Patel RP., 2007. Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis. Free Radical Biology and Medicine. 42(5), 720-729.
    22.
  22. Sasser A.K., Sullivan N.J., Studebaker A.W., Hendey L.F., Axel A.E., Hall B.M., 2007., Interleukin‐6 is a potent growth factor for ER‐α‐positive human breast cancer. The FASEB Journal. 21(13), 3763-37670.
    23.
  23. Schneider B.P., 2005. Angiogenesis of breast cancer. Journal of Clinical Oncology. 23(8), 1782-17890.
    24.
  24. Lijnen R., Maquoi E., Demeulemeester D., Van Hoef B., Collen D., 2002. Modulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity. Thrombosis and Haemostasis. 88(2), 345-353.
    25.
  25. Metheny-barlow L.J., Li L.Y., 2003. The enigmatic role of angiopoietin-1 in tumor angiogenesis. Cell Research. 13(5), 309-317.
    26.
  26. Karkkainen M.J., Haiko P., Sainio K., Partanen J., Taipale J., Petrova T.V., 2004. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nature Immunology. 5(1), 74-80.
    27.
  27. Gavin T., Drew J., Kubik C., Pofahl W., Hickner R., 2007. Acute resistance exercise increases skeletal muscle angiogenic growth factor expression. ACTA Physiologica. 191(2), 139-146.
    28.
  28. Van Hinsbergh V.W., Koolwijk P., 2008. Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovascular Research. 78(2), 203-12.
    29.
  29. Mackey A.L., Donnelly A.E., Turpeenniemi-Hujanen T., Roper H.P., 2004. Skeletal muscle collagen content in humans after high-force eccentric contractions. Journal of Applied Physiology. 97(1), 197-203.
    30.
  30. Rullman E., Norrbom J., Strömberg A., Wågsäter D., Rundqvist H., Haas T., 2009. Endurance exercise activates matrix metalloproteinases in human skeletal muscle. Journal of Applied Physiology. 106(3), 804-812.
    31.
  31. Haas T., Milkiewicz M., Davis S., Zhou A., Egginton S., Brown M., 2000. Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. American Journal of Physiology-Heart and Circulatory Physiology. 279(4), 1540-1547.
    32.
  32. Ma L., Del Soldato P., Wallace J.L., 2002. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: shifting the angiogenic balance. Proceedings of the National Academy of Sciences. 99(20),13243-7.
    33.
  33. Li H., Li S., Shao J., Lin X., Cao Y., Jiang W., 2008. Pharmacokinetic and pharmacodynamic study of intratumoral injection of an adenovirus encoding endostatin in patients with advanced tumors. Gene Therapy. 15(4), 247-256.
    34.
  34. Egginton S., 2009. Invited review: activity-induced angiogenesis. Pflügers Archiv-European Journal of Physiology. 457(5), 963-977.
    35.
  35. Rullman E., Rundqvist H., Wågsäter D., Fischer H., Eriksson P., Sundberg CJ., 2007. A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. Journal of Applied Physiology. 102(6), 2346-23451.
    36.
  36. Kiefer F., Neysari S., Humar R., Li W., Munk V., Battegay E., 2003. Hypertension and angiogenesis. Current Pharmaceutical Design. 9(21), 1733-1744.
    37.
  37. Zarei M., Khazaei M., Sharifi M.R., Pourshanazari AA., 2011. Coronary angiogenesis during experimental hypertension: is it reversible? Journal of Research in Medical Sciences. 16(3), 269-75.
    38.
  38. Hosen S., Dash R., Khatun M., Akter R., Bhuiyan M.H.R., Rezaul M., 2017. In silico ADME/T and 3D QSAR analysis of KDR inhibitors. J Appl Pharm Sci. 7(1),120-128.
    39.
  39. Sane D.C., Anton L., Brosnihan K.B., 2004. Angiogenic growth factors and hypertension. Angiogenesis. 7(3), 193-201.
    40.
  40. Khazaei M., Nematbakhsh M., 2006. Serum level of vascular endothelial growth factor is increased by estrogen replacement therapy in normotensive and DOCA–Salt hypertensive ovariectomized rats. Clinica Chimica Acta. 365(1-2), 206-210.
    41.
  41. Yang R., Ogasawara A.K., Zioncheck T.F., Ren Z., He G.W., DeGuzman G.G., 2002. Exaggerated hypotensive effect of vascular endothelial growth factor in spontaneously hypertensive rats. Hypertension. 39(3), 815-820.
    42.
  42. Pakkir Maideen N.M., 2018. Balasubramaniam R. Pharmacologically relevant drug interactions of sulfonylurea antidiabetics with common herbs. J Herbmed Pharmacol. 7(3):200-210. doi: 10.15171/jhp.2018.32.
    43.
  43. Nazarian-Samani Z., Sewell R.D., Lorigooini Z., Rafieian-Kopaei M., 2018. Medicinal plants with multiple effects on diabetes mellitus and its complications: A Systematic review. Current diabetes reports. 18(10):72.
    44.
  44. Salehi E., Khazaei M., Rashidi B., Javanmard S.H., 2011. Effect of Rosiglitazone on Coronary Angiogenesis in Diabetic and Control Rats. Journal of Isfahan Medical School. 29(134), 386-93
    45.
  45. Vizvari E., Farzanegi P., Abbas Zade Sourati H., 2018. Effect of vigorous aerobic training on serum levels of some inhibitory and excitatory factors of angiogenesis in Women with type 2 diabetes. Pathobiology Research. 21(3), 125-131.
    46.
  46. Ferrari G., Cook B.D., Terushkin V., Pintucci G., Mignatti P., 2009. Transforming growth factor‐beta 1 (TGF‐β1) induces angiogenesis through vascular endothelial growth factor (VEGF)‐mediated apoptosis. Journal of Cellular Physiology. 219(2), 449-458.
    47.
  47. Kuchnio A., Moens S., Bruning U., Kuchnio K., Cruys B., Thienpont B., 2015. The cancer cell oxygen sensor PHD2 promotes metastasis via activation of cancer-associated fibroblasts. Cell Reports. 12(6), 992-1005.
    48.
  48. Rahamooz-Haghighi S., Asadi M.H., 2016. Anti-proliferative effect of  the  extracts  and  essential  oil  of  Pimpinella anisum on gastric cancer cells. J Herbmed Pharmacol. 5(4):157-161
    49.
  49. Taghizadeh E., Taheri F, Abdolkarimi H, Renani P.G., Hayat S.M.G., 2017. Distribution of human papillomavirus genotypes among women in Mashhad, Iran. Intervirology. 60(1-2), 38-42.
    50.
  50. Taghizadeh E., Jahangiri S., Rostami D., Taheri F., Renani P.G., Taghizadeh H., 2019. Roles of E6 and E7 human papillomavirus proteins in molecular pathogenesis of cervical cancer. Current Protein and Peptide Science. 20(9), 926-934.
    51.
  51. Guzman A., Alemany V.S., Nguyen Y., Zhang C.R., Kaufman L.J., 2017. A novel 3D in vitro metastasis model elucidates differential invasive strategies during and after breaching basement membrane. Biomaterials. 115, 19-29.
    52.
  52. Morfoisse F., Kuchnio A., Frainay C., Gomez-Brouchet A., Delisle M.B., Marzi S., 2014. Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1α-independent translation-mediated mechanism. Cell Reports. 6(1), 155-167.
    53.
  53. Redmer D.A., Doraiswamy V., Bortnem B.J., Fisher K., Jablonka-Shariff A., Grazul-Bilska A.T., 2001. Evidence for a role of capillary pericytes in vascular growth of the developing ovine corpus luteum. Biology of Reproduction. 65(3), 879-899.
    54.
  54. Rasooly R.S.G., Gregg J.P., Xiao J.H., 2005. Retinoid X receptor agonists increase Bc12a1 expression and decrease apoptosis of naive T lymphocytes. J Immunol. 175(12), 7916‐7929.
    55.
  55. Hsu S.Y., Lai R., Finegold M., Hsueh A., 1996. Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis. Endocrinology. 137(11), 4837-4843.
    56.
  56. Martínez A., 2006. A new family of angiogenic factors. Cancer letters. 236(2), 157-163.
    57.
  57. Bailo M., Soncini M., Vertua E., Signoroni P.B., Sanzone S., Lombardi G., Arienti D., Calamani F., Zatti D., Paul P., 2004 . Engraftment Potential of Human Amnion and Chorion Cells Derived from Term Placenta. Transplantation. 78(10),1439–1448.
    58.
  58. Cheng C.F., Fan J., Bandyopahdhay B., Mock D., Guan S., Chen M., 2008. Profiling motility signal-specific genes in primary human keratinocytes. Journal of Investigative Dermatology. 128(8), 1981-1990.
    59.
  59. Takahashi M., 2010. Role of the SDF-1/CXCR4 system in myocardial infarction. Circulation Journal. 74(3), 418-23.
    60.
  60. Rafieirad M., Abbaszadeh H., 2017. Pomegranate seed extract reduces ischemia induced anxiety in male rats. J Herbmed Pharmacol. 6(2):85-89.
    61.
  61. O’Neal W., Griffin W., Kent S., Virag J., 2012. Cellular pathways of death and survival in acute myocardial infarction. J Clin Exp Cardiolog S. 6, 003.
    62.
  62. Cencioni C., Capogrossi M.C., Napolitano M., 2012. The SDF-1/CXCR4 axis in stem cell preconditioning. Cardiovascular Research. 94(3), 400-407.
    63.
  63. Satchell S.C., Mathieson P.W., 2003. Angiopoietins: microvascular modulators with potential roles in glomerular pathophysiology. Journal of Nephrology. 16(2), 168-178.
    64.
  64. Leosco D., Rengo G., Iaccarino G., Golino L., Marchese M., Fortunato F., 2008. Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovascular Research. 78(2), 385-394.
    65.
  65. Wu G., Rana J.S., Wykrzykowska J., Du Z., Ke Q., Kang P., 2009. Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 296(2), 385-399.
    66.
  66. Lee S.H., Wolf P.L., Escudero R., Deutsch R., Jamieson S.W., Thistlethwaite P.A., 2000. Early expression of angiogenesis factors in acute myocardial ischemia and infarction. New England Journal of Medicine. 342(9), 626-633.
    67.
  67. Lundby C., Calbet J.A., Robach P., 2009. The response of human skeletal muscle tissue to hypoxia. Cellular and Molecular Life Sciences. 66(22), 3615-3623.
    68.
  68. Zadhoush F., 2012. Physiological role of adenosine and its receptors in tissue hypoxia-induced. Physiology and Pharmacology. 16(3), 209-221.
    69.
  69. Luo Q., Jin P., Li H., Cui K., Jiang T., 2021. Effects of Integrated Health Education Combined with Life Intervention on Patients with Coronary Atherosclerotic Heart Disease Complicated with Hyperlipidemia. American Journal of Health Behavior, 45(5), 843-848.
    70.
  70. Leman M. A., Claramita M., Rahayu G.R., 2021. Predicting Factors on Modeling Health Behavior: A Systematic Review. American Journal of Health Behavior, 45(2), 268-278.
    71.
  71. Rao S., Anthony M.L., Chowdhury N., Kathrotia R., Mishra M., Naithani, M., Singh, N., 2021. Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India. Journal of Carcinogenesis, 20.
    72.
  72. Corches C.L., McBride A.C., Robles M.C., Rehman N., Bailey S., Oliver A., Skolarus, L.E., 2020. Development, adaptation and scale-up of a community-wide, health behavior theory-based stroke preparedness intervention. American Journal of Health Behavior, 44(6), 744-755.
    73.
  73. Susanto A.D., Harahap R.A., Antariksa B, Basalamah M.A., Nurwidya F., 2020. The prevalence and related risk factors of obstructive sleep apnea in heart failure patients at the indonesian referral hospital for respiratory diseases. Journal of Natural Science, Biology and Medicine. 1, 11(2), 164.
    74.
  74. Mahajan K., Kandoria A., Bhardwaj R., Negi P.C., Asotra S., Gupta G., 2019. Clinical and coronary angiographic profile in women presenting with anginal chest pain: Results from a single-center prospective observational study. Journal of Natural Science, Biology and Medicine, 10(1), 60.
    75.
  75. Abid H., Abid Z., Abid, S., 2021. Atherogenic indices in clinical practice and biomedical research: A short review: Atherogenic indices and cardiovascular diseases. Baghdad Journal of Biochemistry and Applied Biological Sciences, 2(02), 59-69.
    76.
  76. Othman Z., Khalep, H.R.H., Abidin A.Z., Hassan H., Fattepur, S., 2019. The Anti-Angiogenic Properties of Morinda citrifolia. L (Mengkudu) Leaves Using Chicken Chorioallantoic Membrane (CAM) Assay. Pharmacognosy Journal, 11(1), 6.
    77.
  77. Wardani H.A., Rahmadi M., Ardianto C., Balan S.S., Kamaruddin N.S., Khotib J., 2019. Development of nonalcoholic fatty liver disease model by high-fat diet in rats. Journal of basic and clinical physiology and pharmacology, 30(6), 3.
    78.
  78. Paul R., Mukkadan J.K., 2020. Modulation of blood glucose, oxidative stress, and anxiety level by controlled vestibular stimulation in prediabetes. Journal of Natural Science, Biology and Medicine, 11(2), 111.
    79.
  79. Zhang Y., Mahdavi B., Mohammadhosseini M., Rezaei-Seresht E., Paydarfard S., Qorbani M., Karimian M., Abbasi N., Ghaneialvar H., Karimi E., 2021. Green synthesis of NiO nanoparticles using Calendula officinalis extract: Chemical charactrization, antioxidant, cytotoxicity, and anti-esophageal carcinoma properties. Arabian Journal of Chemistry. 14(5), 103105.
    80.
  80. Ma D., Han T., Karimian M., Abbasi N., Ghaneialvar H., Zangeneh A., 2020. Immobilized Ag NPs on chitosan-biguanidine coated magnetic nanoparticles for synthesis of propargylamines and treatment of human lung cancer. International Journal of Biological Macromolecules. 165, 767-775.
    81.
  81. Manouchehri A., Shakib P., Biglaryan F., Nazer M., Darvishi M., 2021. The most important medicinal plants affecting bee stings: A systematic review study. Uludag Aricilik Dergisi. 21(1), 91-103.
    82.

 

Related articles

The rights to this website are owned by the Raimag Press Management System.
Copyright © 2021-2024

Home| Login| About Us| Contact Us|
[فارسی] [العربية] [fa] [ar]