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Role of Lymphangiogenesis in Cardiac Repair and Regeneration Cover

Role of Lymphangiogenesis in Cardiac Repair and Regeneration

Open Access
|Nov 2023

References

  1. Sadek H, Olson EN. Toward the Goal of Human Heart Regeneration. Cell Stem Cell. 2020;26(1):7-16. Epub 2020/01/07. doi: 10.1016/j.stem.2019.12.004
  2. Zhang Y, Bai Y, Jing Q, Qian J. Functions and Regeneration of Mature Cardiac Lymphatic Vessels in Atherosclerosis, Myocardial Infarction, and Heart Failure. Lymphat Res Biol. 2018;16(6):507-15. Epub 2018/10/20. doi: 10.1089/lrb.2018.0023
  3. Frangogiannis NG. Pathophysiology of Myocardial Infarction. Compr Physiol. 2015;5(4):1841-75. Epub 2015/10/02. doi: 10.1002/cphy.c150006
  4. Duhon BH, Phan TT, Taylor SL, Crescenzi RL, Rutkowski JM. Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis. Int J Mol Sci. 2022;23(12). Epub 2022/06/25. doi: 10.3390/ijms23126621
  5. Brakenhielm E, Gonzalez A, Diez J. Role of Cardiac Lymphatics in Myocardial Edema and Fibrosis: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;76(6):735-44. Epub 2020/08/09. doi: 10.1016/j.jacc.2020.05.076
  6. Chen K, Mou R, Zhu P, Xu X, Wang H, Jiang L, et al. The Effect of Lymphangiogenesis in Transplant Arteriosclerosis. Circulation. 2023;147(6):482-97. Epub 2022/12/15. doi: 10.1161/CIRCULATIONAHA.122.060799
  7. Klaourakis K, Vieira JM, Riley PR. The evolving cardiac lymphatic vasculature in development, repair and regeneration. Nat Rev Cardiol. 2021;18(5):368-79. Epub 2021/01/20. doi: 10.1038/s41569-020-00489-x
  8. Sacchi G, Weber E, Agliano M, Cavina N, Comparini L. Lymphatic vessels of the human heart: precollectors and collecting vessels. A morpho-structural study. J Submicrosc Cytol Pathol. 1999;31(4):515-25. Epub 2000/02/24. PubMed PMID: 10685392
  9. Shimada T, Morita T, Oya M, Kitamura H. Morphological studies of the cardiac lymphatic system. Arch Histol Cytol. 1990;53 Suppl:115-26. Epub 1990/01/01. doi: 10.1679/aohc.53.suppl_115
  10. Sacchi G, Weber E, Agliano M, Raffaelli N, Comparini L. The structure of superficial lymphatics in the human thigh: precollectors. Anat Rec. 1997;247(1):53-62. Epub 1997/01/01. doi: 10.1002/(SICI)1097-0185(199701)247:1<;53::AID-AR8>3.0.CO;2-G
  11. Houssari M, Dumesnil A, et al. Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2020;40(7):1722-37. Epub 2020/05/15. doi: 10.1161/ATVBAHA.120.314370
  12. Klotz L, Norman S, Vieira JM, et al. Cardiac lymphatics are heterogeneous in origin and respond to injury. Nature. 2015;522(7554):62-7. Epub 2015/05/21. doi: 10.1038/nature14483
  13. Flaht-Zabost A, Gula G, Ciszek B, et al. Cardiac mouse lymphatics: developmental and anatomical update. Anat Rec (Hoboken). 2014;297(6):1115-30. Epub 2014/04/05. doi: 10.1002/ar.22912
  14. Taira A, Morishita Y, Arikawa K, Murata K, Hamada Y, Akita H. Flow velocity of cardiac lymph and contractility of the heart: an experimental study. Ann Thorac Surg. 1977;23(3):230-4. Epub 1977/03/01. doi: 10.1016/s0003-4975(10)64114-8
  15. Ullal SR, Kluge TH, Kerth WJ, Gerbode F. Flow and composition of cardiac lymph in dogs. Ann Surg. 1972;175(3):299-304. Epub 1972/03/01. doi: 10.1097/00000658-197203000-00001
  16. Jankowska-Steifer E, Ratajska A, Czarnowska E, et al. Assessing functional status of cardiac lymphatics: From macroscopic imaging to molecular profiling. Trends Cardiovasc Med. 2021;31(6):333-8. Epub 2020/06/28. doi: 10.1016/j.tcm.2020.06.006
  17. Moore JE Jr, Bertram CD. Lymphatic System Flows. Annu Rev Fluid Mech. 2018;50:459-82. Epub 2018/05/02. doi: 10.1146/annurev-fluid-122316-045259
  18. Scallan JP, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016;594(20):5749-68. Epub 2016/05/25. doi: 10.1113/JP272088
  19. Brakenhielm E, Alitalo K. Cardiac lymphatics in health and disease. Nat Rev Cardiol. 2019;16(1):56-68. Epub 2018/10/20. doi: 10.1038/s41569-018-0087-8
  20. Kholova I, Dragneva G, Cermakova P, et al. Lymphatic vasculature is increased in heart valves, ischaemic and inflamed hearts and in cholesterol-rich and calcified atherosclerotic lesions. Eur J Clin Invest. 2011;41(5):487-97. Epub 2010/12/07. doi: 10.1111/j.1365-2362.2010.02431.x
  21. Loukas M, Abel N, Tubbs RS, Grabska J, Birungi J, Anderson RH. The cardiac lymphatic system. Clin Anat. 2011;24(6):684-91. Epub 2011/03/10. doi: 10.1002/ca.21104
  22. Ratajska A, Gula G, Flaht-Zabost A, et al. Comparative and developmental anatomy of cardiac lymphatics. ScientificWorldJournal. 2014 Jan 27;2014:183170. Epub 2014/03/05. doi: 10.1155/2014/183170
  23. Golab B. Lymphatic vessels of the conducting system of human heart. Folia Morphol (Warsz). 1977;36(4):317-22. Epub 1977/01/01. PMID: 306948
  24. Huang LH, Lavine KJ, Randolph GJ. Cardiac Lymphatic Vessels, Transport, and Healing of the Infarcted Heart. JACC Basic Transl Sci. 2017;2(4):477-83. Epub 2017/10/11. doi: 10.1016/j.jacbts.2017.02.005
  25. Henri O, Pouehe C, Houssari M, et al. Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction. Circulation. 2016;133(15):1484-97; discussion 97. Epub 2016/03/05. doi: 10.1161/CIRCULATIONAHA.115.020143
  26. Eliska O, Eliskova M, Miller AJ. The absence of lymphatics in normal and atherosclerotic coronary arteries in man: a morphologic study. Lymphology. 2006;39(2):76-83. Epub 2006/08/17. PMID: 16910098
  27. Shimizu Y, Polavarapu R, Eskla KL, et al. Impact of Lymphangiogenesis on Cardiac Remodeling After Ischemia and Reperfusion Injury. J Am Heart Assoc. 2018;7(19):e009565. Epub 2018/10/30. doi: 10.1161/JAHA.118.009565. PubMed PMID
  28. Johnson LA, Prevo R, Clasper S, Jackson DG. Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. J Biol Chem. 2007;282(46):33671-80. Epub 2007/09/22. doi: 10.1074/jbc.M702889200
  29. Vieira JM, Norman S, Villa Del Campo C, et al. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest. 2018;128(8):3402-12. Epub 2018/07/10. doi: 10.1172/JCI97192
  30. Vuorio T, Yla-Herttuala E, Laakkonen JP, Laidinen S, Liimatainen T, Yla-Herttuala S. Downregulation of VEGFR3 signaling alters cardiac lymphatic vessel organization and leads to a higher mortality after acute myocardial infarction. Sci Rep. 2018;8(1):16709. Epub 2018/11/14. doi: 10.1038/s41598-018-34770-4
  31. Frantz S, Hofmann U, Fraccarollo D, et al. Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction. FASEB J. 2013;27(3):871-81. Epub 2012/11/20. doi: 10.1096/fj.12-214049
  32. Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204(12):3037-47. Epub 2007/11/21. doi: 10.1084/jem.20070885
  33. van Amerongen MJ, Harmsen MC, van Rooijen N, Petersen AH, van Luyn MJ. Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol. 2007;170(3):818-29. Epub 2007/02/27. doi: 10.2353/ajpath.2007.060547
  34. Liu X, Cui K, Wu H, et al. Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases. Arterioscler Thromb Vasc Biol. 2023;43(1):e1-e10. Epub 2022/12/02. doi: 10.1161/ATVBAHA.122.318406
  35. Trincot CE, Xu W, Zhang H, et al. Adrenomedullin Induces Cardiac Lymphangiogenesis After Myocardial Infarction and Regulates Cardiac Edema Via Connexin 43. Circ Res. 2019;124(1):101-13. Epub 2018/12/26. doi: 10.1161/CIRCRESAHA.118.313835
  36. Tatin F, Renaud-Gabardos E, Godet AC, et al. Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction. JCI Insight. 2017;2(12). Epub 2017/06/15. doi: 10.1172/jci.insight.93887
  37. Rucker AJ, Rudemiller NP, Crowley SD. Salt, Hypertension, and Immunity. Annu Rev Physiol. 2018;80:283-307. Epub 2017/11/18. doi: 10.1146/annurev-physiol-021317-121134
  38. Jhee JH, Park HC, Choi HY. Skin Sodium and Blood Pressure Regulation. Electrolyte Blood Press. 2022;20(1):1-9. Epub 2022/12/02. doi: 10.5049/EBP.2022.20.1.1
  39. Nosalski R, Guzik TJ. Skin sodium, lymphatics, and blood pressure: a non-canonical mechanism of salt-sensitive hypertension. Eur Heart J. 2023;44(29):2743-5. Epub 2023/06/28. doi: 10.1093/eurheartj/ehad290
  40. Chachaj A, Szuba A. Skin lymphatic system in the pathogenesis of arterial hypertension - review and critique. Lymphology. 2020;53(3):99-108. Epub 2020/12/23. PMID: 33350284
  41. Wiig H, Luft FC, Titze JM. The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis. Acta Physiol (Oxf). 2018;222(3). Epub 2017/12/02. doi: 10.1111/apha.13006
  42. Johnson RS, Titze J, Weller R. Cutaneous control of blood pressure. Curr Opin Nephrol Hypertens. 2016;25(1):11-5. Epub 2015/12/03. doi: 10.1097/MNH.0000000000000188
  43. Glinton KE, Ma W, Lantz C, et al. Macrophage-produced VEGFC is induced by efferocytosis to ameliorate cardiac injury and inflammation. J Clin Invest. 2022;132(9). Epub 2022/03/11. doi: 10.1172/JCI140685
  44. Justin Rucker A, Crowley SD. The role of macrophages in hypertension and its complications. Pflugers Arch. 2017;469(3-4):419-30. Epub 2017/03/03. doi: 10.1007/s00424-017-1950-x
  45. Lankhorst S, Severs D, Marko L, et al. Salt Sensitivity of Angiogenesis Inhibition-Induced Blood Pressure Rise: Role of Interstitial Sodium Accumulation? Hypertension. 2017;69(5):919-26. Epub 2017/03/23. doi: 10.1161/HYPERTENSIONAHA.116.08565
  46. Zhuang T, Lei Y, Chang JJ, et al. A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension. Eur Heart J. 2023;44(29):2730-42. Epub 2023/06/28. doi: 10.1093/eurheartj/ehad377
  47. Johnson RA. The lymphatic system of the heart. Lymphology. 1969;2(3):95-108. Epub 1969/09/01. PMID: 5823723
  48. Miller AJ, Pick R, Katz LN. Lymphatics of the mitral valve of the dog. Demonstration and discussion of the possible significance. Circ Res. 1961;9:1005-9. Epub 1961/09/01. doi: 10.1161/01.res.9.5.1005
  49. Niinimaki E, Mennander AA, Paavonen T, Kholova I. Lymphangiogenesis is increased in heart valve endocarditis. Int J Cardiol. 2016;219:317-21. Epub 2016/06/28. doi: 10.1016/j.ijcard.2016.06.049
  50. Dieterich LC, Seidel CD, Detmar M. Lymphatic vessels: new targets for the treatment of inflammatory diseases. Angiogenesis. 2014;17(2):359-71. Epub 2013/11/12. doi: 10.1007/s10456-013-9406-1
  51. Halin C, Tobler NE, Vigl B, Brown LF, Detmar M. VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes. Blood. 2007;110(9):3158-67. Epub 2007/07/13. doi: 10.1182/blood-2007-01-066811
  52. Wirzenius M, Tammela T, Uutela M, et al. Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med. 2007;204(6):1431-40. Epub 2007/05/31. doi: 10.1084/jem.20062642
  53. Patel R. New Developments in Clinical Bacteriology Laboratories. Mayo Clin Proc. 2016;91(10):1448-59. Epub 2016/08/25. doi: 10.1016/j.mayocp.2016.06.020
  54. Edwards LA, Nowocin AK, Jafari NV, et al. Chronic Rejection of Cardiac Allografts Is Associated With Increased Lymphatic Flow and Cellular Trafficking. Circulation. 2018;137(5):488-503. Epub 2017/08/05. doi: 10.1161/CIRCULATIONAHA.117.028533
  55. Ji RC. The role of lymphangiogenesis in cardiovascular diseases and heart transplantation. Heart Fail Rev. 2022;27(5):1837-56. Epub 2021/11/05. doi: 10.1007/s10741-021-10188-5
  56. Wong BW. Lymphatic vessels in solid organ transplantation and immunobiology. Am J Transplant. 2020;20(8):1992-2000. Epub 2020/02/07. doi: 10.1111/ajt.15806
  57. Daly KP, Seifert ME, Chandraker A, et al. VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2013;32(1):120-8. Epub 2012/12/25. doi: 10.1016/j.healun.2012.09.030
  58. Jones D, Min W. An overview of lymphatic vessels and their emerging role in cardiovascular disease. J Cardiovasc Dis Res. 2011;2(3):141-52. Epub 2011/10/25. doi: 10.4103/0975-3583.85260
  59. Cursiefen C, Cao J, Chen L, et al. Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival. Invest Ophthalmol Vis Sci. 2004;45(8):2666-73. Epub 2004/07/28. doi: 10.1167/iovs.03-1380
  60. Nykanen AI, Sandelin H, Krebs R, et al. Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation. 2010;121(12):1413-22. Epub 2010/03/17. doi: 10.1161/CIRCULATIONAHA.109.910703
  61. Dashkevich A, Raissadati A, Syrjala SO, et al. Ischemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts. Am J Transplant. 2016;16(4):1160-72. Epub 2015/12/23. doi: 10.1111/ajt.13564
  62. Cui Y, Liu K, Monzon-Medina ME, et al. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection. J Clin Invest. 2015;125(11):4255-68. Epub 2015/10/21. doi: 10.1172/JCI79693
  63. Kelly B, Mohanakumar S, Hjortdal VE. Diagnosis and Management of Lymphatic Disorders in Congenital Heart Disease. Curr Cardiol Rep. 2020;22(12):164. Epub 2020/10/11. doi: 10.1007/s11886-020-01405-y
  64. Savla JJ, Itkin M, Rossano JW, Dori Y. Post-Operative Chylothorax in Patients With Congenital Heart Disease. J Am Coll Cardiol. 2017;69(19):2410-22. Epub 2017/05/13. doi: 10.1016/j.jacc.2017.03.021
  65. Tabib A, Talebi T, Ghasemi S, et al. A novel stop-gain pathogenic variant in FLT4 and a nonsynonymous pathogenic variant in PTPN11 associated with congenital heart defects. Eur J Med Res. 2022;27(1):286. Epub 2022/12/11. doi: 10.1186/s40001-022-00920-8
  66. Monaghan RM, Page DJ, Ostergaard P, Keavney BD. The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases. Cardiovasc Res. 2021;117(8):1877-90. Epub 2020/10/18. doi: 10.1093/cvr/cvaa291
  67. Heron C, Dumesnil A, Houssari M, et al. Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure. Cardiovasc Res. 2023;119(2):492-505. Epub 2022/06/12. doi: 10.1093/cvr/cvac086
  68. Ranjbarvaziri S, Kooiker KB, Ellenberger M, et al. Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy. Circulation. 2021;144(21):1714-31. Epub 2021/10/22. doi: 10.1161/CIRCULATIONAHA.121.053575
  69. Wang YL, Wang XH, Liu YL, Kong XQ, Wang LX. Cardiac lymphatic obstruction impairs left ventricular function and increases plasma endothelin-1 and angiotensin II in rabbits. Lymphology. 2009;42(4):182-7. Epub 2010/03/12. PMID: 20218086
  70. Fantl P, Nelson JF. Coagulation in lymph. J Physiol. 1953;122(1):33-7. Epub 1953/10/01. doi: 10.1113/jphysiol.1953.sp004976
  71. Bizou M, Itier R, Majdoubi M, et al. Cardiac macrophage subsets differentially regulate lymphatic network remodeling during pressure overload. Sci Rep. 2021;11(1):16801. Epub 2021/08/21. doi: 10.1038/s41598-021-95723-y
  72. Huusko J, Lottonen L, Merentie M, et al. AAV9-mediated VEGF-B gene transfer improves systolic function in progressive left ventricular hypertrophy. Mol Ther. 2012;20(12):2212-21. Epub 2012/10/24. doi: 10.1038/mt.2012.145
  73. Abraham D, Hofbauer R, Schafer R, et al. Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy. Circ Res. 2000;87(8):644-7. Epub 2000/10/13. doi: 10.1161/01.res.87.8.644
  74. Guertl B, Noehammer C, Hoefler G. Metabolic cardiomyopathies. Int J Exp Pathol. 2000;81(6):349-72. Epub 2001/04/12. doi: 10.1046/j.1365-2613.2000.00186.x
  75. Zweifach BW, Prather JW. Micromanipulation of pressure in terminal lymphatics in the mesentery. Am J Physiol. 1975;228(5):1326-35. Epub 1975/05/01. doi: 10.1152/ajplegacy.1975.228.5.1326
  76. Purwowiyoto SL, Prawara AS. Metabolic syndrome and heart failure: mechanism and management. Med Pharm Rep. 2021;94(1):15-21. Epub 2021/02/26. doi: 10.15386/mpr-1884
  77. Cuijpers I, Simmonds SJ, van Bilsen M, et al. Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities. Basic Res Cardiol. 2020;115(4):39. Epub 2020/05/27. doi: 10.1007/s00395-020-0798-y
  78. Saito E, Isogai S, Deguchi T, et al. Intraperitoneal dye injection method for visualizing the functioning lymphatic vascular system in zebrafish and medaka. Dev Dyn. 2020;249(5):679-92. Epub 2019/12/15. doi: 10.1002/dvdy.143
  79. Ugander M, Bagi PS, Oki AJ, et al. Myocardial edema as detected by pre-contrast T1 and T2 CMR delineates area at risk associated with acute myocardial infarction. JACC Cardiovasc Imaging. 2012;5(6):596-603. Epub 2012/06/16. doi: 10.1016/j.jcmg.2012.01.016
DOI: https://doi.org/10.14797/mdcvj.1286 | Journal eISSN: 1947-6108
Language: English
Page range: 37 - 46
Submitted on: Aug 30, 2023
Accepted on: Sep 15, 2023
Published on: Nov 16, 2023
Published by: Houston Methodist DeBakey Heart & Vascular Center
In partnership with: Paradigm Publishing Services

© 2023 Zhongyun Xu, Qing Lu, Liming Chen, Chengchao Ruan, Yingnan Bai, Yunzeng Zou, Junbo Ge, published by Houston Methodist DeBakey Heart & Vascular Center
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.