Molecular and Cellular Aspects of Endothelial-Mesenchymal Transition in Cardiovascular Diseases

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Somente assinantes

Resumo

Endothelial cells (ECs), which form the inner surface of the blood vessels, contact with blood, withstand mechanical pressure, and demonstrate heterogeneous reactions to exogenous and endogenous stimuli. ECs have unique properties in accordance with their niche, and play an important role in regulating vascular homeostasis. Endothelial cells may undergo a dynamic phenotypic switch in terms of its heterogeneity, which may lead to endothelial dysfunction and a number of associated pathologies. Endothelial-mesenchymal transition (EndMT) is one of the possible molecular and cellular mechanisms of such kind. EndMT is characterized by phenotypic changes in ECs through which the cells obtain new properties, i.e. start producing mesenchymal markers such as alpha-SMA and vimentin, change morphology, and become able to migrate. EndMT is a complex biological process, which may be induced by inflammation, hypoxia or oxidative stress, and be involved in pathogenesis of cardiovascular disease. This manuscript presents the key markers, inhibitors, inducers of endothelial-mesenchymal transition, and overall state-of-the-art of EndMT in cardiovascular diseases.

Sobre autores

E. Strelnikova

Ryazan State Medical University

Email: ekaterina3333@rambler.ru
Russia, 390026, Ryazan

R. Kalinin

Ryazan State Medical University

Email: ekaterina3333@rambler.ru
Russia, 390026, Ryazan

I. Suchkov

Ryazan State Medical University

Email: ekaterina3333@rambler.ru
Russia, 390026, Ryazan

N. Korotkova

Ryazan State Medical University

Email: ekaterina3333@rambler.ru
Russia, 390026, Ryazan

N. Mzhavanadze

Ryazan State Medical University

Autor responsável pela correspondência
Email: ekaterina3333@rambler.ru
Russia, 390026, Ryazan

Bibliografia

  1. Rodrigues S.F., Granger D.N. (2015) Blood cells and endothelial barrier function. Tissue Barriers. 3(1–2), e978720.
  2. Калинин Р.Е., Сучков И.А., Крылов А.А., Мжаванадзе Н.Д., Пшенников А.С., Соляник Н.А., Герасимов А.А. (2021) Комплексный подход к лечению неоперабельных пациентов с критической ишемией нижних конечностей и сахарным диабетом: результаты и перспективы. Наука молодых – Eruditio Juvenium. 9(4), 559‒572.
  3. Pérez L., Muñoz-Durango N., Riedel C.A., Echeverría C., Kalergis A.M., Cabello-Verrugio C., Simon F. (2017) Endothelial-to-mesenchymal transition: cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions. Cytokine Growth Factor Rev. 33, 41‒54.
  4. Kizu A., Medici D., Kalluri R. (2009). Endothelial–mesenchymal transition as a novel mechanism for generating myofibroblasts during diabetic nephropathy. Am. J. Pathol. 175(4), 1371‒1373.
  5. Souilhol C., Harmsen M.C., Evans P.C., Krenning G. (2018) Endothelial–mesenchymal transition in atherosclerosis. Cardiovascular Res. 114(4), 565‒577.
  6. Kokudo T., Suzuki Y., Yoshimatsu Y., Yamazaki T., Watabe T., Miyazono K. (2008) Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J. Cell Sci. 121(20), 3317‒3324.
  7. Kovacic J.C., Dimmeler S., Harvey R.P., Finkel T., Aikawa E., Krenning G., Baker A.H. (2019) Endothelial to mesenchymal transition in cardiovascular disease: JACC state-of-the-art review. J. Am. College Cardiol. 73(2), 190‒209.
  8. Zhang Y., Zhang M., Xie W., Wan J., Tao X., Liu M., Zhen Y., Lin F., Wu B., Zhai Z., Wang C. (2020) Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells. Exp. Cell Res. 390(1), 111941.
  9. Liao D., Sundlov J., Zhu J., Mei H., Hu Y., Newman D.K., Newman P.J. (2022) Atomic level dissection of the platelet endothelial cell adhesion molecule 1 (PECAM-1) homophilic binding interface: implications for endothelial cell barrier function. Arterioscler. Thromb. Vasc. Biol. 42(2), 193‒204.
  10. Sadler J.E. (1998) Biochemistry and genetics of von Willebrand factor. Annu. Rev. Biochem. 67, 395.
  11. Van Roy F., Berx G. (2008) The cell-cell adhesion molecule E-cadherin. Cell. Mol. Life Sci. 65(23), 3756‒3788.
  12. Harris E.S., Nelson W.J. (2010). VE-cadherin: at the front, center, and sides of endothelial cell organization and function. Curr. Opin. Cell Biol. 22(5), 651‒658.
  13. Herrmann H., Hesse M., Reichenzeller M., Aebi U., Magin T.M. (2002) Functional complexity of intermediate filament cytoskeletons: from structure to assembly to gene ablation. Int. Rev. Cytol. 223, 83‒175.
  14. Colucci-Guyon E., Portier M.M., Dunia I., Paulin D., Pournin S., Babinet C. (1994) Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell. 79(4), 679‒694.
  15. Colucci-Guyon E., Giménez Y., Ribotta M., Maurice T., Babinet C., Privat A. (1999) Cerebellar defect and impaired motor coordination in mice lacking vimentin. Glia. 25(1), 33‒43.
  16. Eckes B., Colucci-Guyon E., Smola H., Nodder S., Babinet C., Krieg T., Martin P. (2000) Impaired wound healing in embryonic and adult mice lacking vimentin. J. Cell Sci. 113(13), 2455‒2462.
  17. Henrion D., Terzi F., Matrougui K., Duriez M., Boulanger C.M., Colucci-Guyon E., Babinet C., Briand P., Friedlander G., Poitevin P., Lévy B.I. (1997) Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J. Clin. Invest. 100(11), 2909‒2914.
  18. Veres-Székely A., Pap D., Sziksz E., Jávorszky E., Rokonay R., Lippai R., Tony K., Fekete A., Tulassay T., Szabo A.J., Vannay Á. (2017) Selective measurement of α smooth muscle actin: why β-actin can not be used as a housekeeping gene when tissue fibrosis occurs. BMC Mol. Biol. 18(1), 1‒15.
  19. Doherty G.J., McMahon H.T. (2008) Mediation, modulation, and consequences of membrane-cytoskeleton interactions. Annu. Rev. Biophys. 37(1), 65‒95.
  20. Samad F., Loskutoff D.J. (1996) Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol. Med. 2(5), 568‒582.
  21. Vaughan D.E. (2005) PAI-1 and atherothrombosis. J. Thrombosis Haemostasis. 3(8), 1879‒1883.
  22. Rana T., Jiang C., Liu G., Miyata T., Antony V., Thannickal V.J., Liu R.M. (2020) PAI-1 regulation of TGF-β1-induced alveolar type II cell senescence, SASP secretion, and SASP-mediated activation of alveolar macrophages. Am. J. Respir. Cell Mol. Biol. 62(3), 319‒330.
  23. Fukudome K., Esmon C.T. (1994) Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J. Biol. Chem. 269(42), 26486‒26491.
  24. Wharton K., Derynck R. (2009) TGFβ family signaling: novel insights in development and disease. Development. 136(22), 3691‒3697.
  25. Farrar E.J., Butcher J.T. (2014) Heterogeneous susceptibility of valve endothelial cells to mesenchymal transformation in response to TNFα. Ann. Biomed. Eng. 42(1), 149‒161.
  26. Romero L.I., Zhang D.N., Herron G.S., Karasek M.A. (1997). Interleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells. J. Cell. Physiol. 173(1), 84‒92.
  27. Maleszewska M., Gjaltema R.A., Krenning G., Harmsen M.C. (2015) Enhancer of zeste homolog-2 (EZH2) methyltransferase regulates transgelin/smooth muscle-22α expression in endothelial cells in response to interleukin-1β and transforming growth factor-β2. Cell. Signal. 27(8), 1589‒1596.
  28. Cho J.G., Lee A., Chang W., Lee M.S., Kim J. (2018) Endothelial to mesenchymal transition represents a key link in the interaction between inflammation and endothelial dysfunction. Front. Immunol. 9, 294.
  29. Good R.B., Gilbane A.J., Trinder S.L., Denton C.P., Coghlan G., Abraham D.J., Holmes A.M. (2015) Endothelial to mesenchymal transition contributes to endothelial dysfunction in pulmonary arterial hypertension. Am. J. Pathol. 185(7), 1850‒1858.
  30. Lee J.G., Ko M.K., Kay E.P. (2012) Endothelial mesenchymal transformation mediated by IL-1β-induced FGF-2 in corneal endothelial cells. Exp. Eye Res. 95(1), 35‒39.
  31. Dejana E., Hirschi K.K., Simons M. (2017) The molecular basis of endothelial cell plasticity. Nat. Commun. 8(1), 1‒11.
  32. Sabbineni H., Verma A., Artham S., Anderson D., Amaka O., Liu F., Narayanan S.P., Somanath P.R. (2019) Pharmacological inhibition of β-catenin prevents EndMT in vitro and vascular remodeling in vivo resulting from endothelial Akt1 suppression. Biochem. Pharmacol. 164, 205‒215.
  33. Giordo R., Ahmed Y.M., Allam H., Abusnana S., Pappalardo L., Nasrallah G.K., Mangoni A.A., Pintus G. (2021) EndMT regulation by small RNAs in diabetes-associated fibrotic conditions: potential link with oxidative stress. Front. Cell Develop. Biol. 9, 683594.
  34. Shang J., Zhang Y., Jiang Y., Li Z., Duan Y., Wang L., Xiao J., Zhao Z. (2017) NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy. Biochem. Biophys. Res. Commun. 484(2), 435‒441.
  35. Zhao L., Zhao J., Wang X., Chen Z., Peng K., Lu X., Meng L., Liu G., Guan G., Wang F. (2016) Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy. Physiol. Genomics. 48(10), 711‒718.
  36. Ma Z., Zhu L., Liu Y., Wang Z., Yang Y., Chen L., Lu Q. (2017) Lovastatin alleviates endothelial-to-mesenchymal transition in glomeruli via suppression of oxidative stress and TGF-β1 signaling. Front. Pharmacol. 8, 473.
  37. Chen P.Y., Qin L., Barnes C., Charisse K., Yi T., Zhang X., Ali R., Medina P.P., Yu J., Slack F.J., Anderson D.J., Kotelianski V., Wang F., Tellides G., Simons M. (2012) FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Rep. 2(6), 1684‒1696.
  38. Ichise T., Yoshida N., Ichise H. (2014) FGF2-induced Ras–MAPK signalling maintains lymphatic endothelial cell identity by upregulating endothelial-cell-specific gene expression and suppressing TGFβ signalling through Smad2. J. Cell Sci. 127(4), 845‒857.
  39. Xu X., Friehs I., Zhong Hu T., Melnychenko I., Tampe B., Alnour F., Iasconr M., Kalluri R., Zeisberg M., del Nido P.J., Zeisberg E.M. (2015) Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition. Circulation Res. 116(5), 857‒866.
  40. Kanasaki K., Shi S., Kanasaki M., He J., Nagai T., Nakamura Y., Ishidaki Y., Kitada M., Srivastava S.P., Koya D. (2014) Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 63(6), 2120‒2131.
  41. Gao H., Zhang J., Liu T., Shi W. (2011) Rapamycin prevents endothelial cell migration by inhibiting the endothelial-to-mesenchymal transition and matrix metalloproteinase-2 and-9: an in vitro study. Mol. Vision. 17, 3406.
  42. Cipriani P., Di Benedetto P., Ruscitti P., Capece D., Zazzeroni F., Liakouli V., Pantano I., Berardicurti O., Carubbi F., Pecetti G., Turricchia S., Edoardo Alesse, Iglarz M., Giacomelli R. (2015) The endothelial-mesenchymal transition in systemic sclerosis is induced by endothelin-1 and transforming growth factor-β and may be blocked by macitentan, a dual endothelin-1 receptor antagonist. J. Rheumatol. 42(10), 1808‒1816.
  43. Guo Y., Li P., Bledsoe G., Yang Z.R., Chao L., Chao J. (2015) Kallistatin inhibits TGF-β-induced endothelial–mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. Exp. Cell Res. 337(1), 103‒110.
  44. Chen X., Cai J., Zhou X., Chen L., Gong Y., Gao Z., Zhang H., Huang W., Zhou H. (2015) Protective effect of spironolactone on endothelial-to-mesenchymal transition in HUVECs via notch pathway. Cell. Physiol. Biochem. 36(1), 191‒200.
  45. Wylie-Sears J., Levine R.A., Bischoff J. (2014) Losartan inhibits endothelial-to-mesenchymal transformation in mitral valve endothelial cells by blocking transforming growth factor-β-induced phosphorylation of ERK. Biochem. Biophys. Res. Commun. 446(4), 870‒875.
  46. Testai L., Brancaleone V., Flori L., Montanaro R., Calderone V. (2021) Modulation of EndMT by hydrogen sulfide in the prevention of cardiovascular fibrosis. Antioxidants. 10(6), 910.
  47. Lovisa S., Fletcher-Sananikone E., Sugimoto H., Hensel J., Lahiri S., Hertig A., Taburi G., Lawson E., Dewar R., Revuelta I., Kato N., Wu C.J., Bassett J.R.R.L., Putluni N., Zeisberg M., Zeisberg E.M., Lebleu V., Kalluri R. (2020) Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis. Sci. Signal. 13(635), eaaz2597.
  48. Manetti M., Romano E., Rosa I., Guiducci S., Bellando-Randone S., De Paulis A., Ibba-Manneschi L., Matucci-Cerinic M. (2017) Endothelial-to-mesenchymal transition contributes to endothelial dysfunction and dermal fibrosis in systemic sclerosis. Ann. Rheum. Dis. 76(5), 924‒934.
  49. Hao Y.M., Yuan H.Q., Ren Z., Qu S.L., Liu L.S., Yin K., Yin K., Fu M., Jiang Z.S. (2019) Endothelial to mesenchymal transition in atherosclerotic vascular remodeling. Clin. Chim. Acta. 490, 34‒38.
  50. Gorelova A., Berman M., Al Ghouleh I. (2021) Endothelial-to-mesenchymal transition in pulmonary arterial hypertension. Antioxid. Redox Signal. 34(12), 891‒914.
  51. Gurzu S., Kobori L., Fodor D., Jung I. (2019) Epithelial mesenchymal and endothelial mesenchymal transitions in hepatocellular carcinoma: a review. BioMed Res. Int. 2019. 2962580.
  52. van Nieuw Amerongen G.P., van Hinsbergh V.W. (2002). Targets for pharmacological intervention of endothelial hyperpermeability and barrier function. Vasc. Pharmacol. 39(4‒5), 257‒272.
  53. Barabutis N., Verin A., Catravas J.D. (2016) Regulation of pulmonary endothelial barrier function by kinases. Am. J. Physiol. ‒ Lung Cell. Mol. Physiol. 311(5), L832‒L845.
  54. Davignon J., Ganz P. (2004) Role of endothelial dysfunction in atherosclerosis. Circulation. 109(23 Suppl 1). III27-32.
  55. Mudau M., Genis A., Lochner A., Strijdom H. (2012) Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc. J. Africa. 23(4), 222‒231.
  56. Chang J.C., Kou S.J., Lin W.T., Liu C.S. (2010) Regulatory role of mitochondria in oxidative stress and atherosclerosis. World J. Cardiol. 2(6), 150.
  57. Moonen J.R.A., Lee E.S., Schmidt M., Maleszewska M., Koerts J.A., Brouwer L.A., van Kooter T.G., van Luyn M.J.A., Zeebregts C.J., Krenning G., Harmsen M.C. (2015) Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovasc. Res. 108(3), 377‒386.
  58. Ma K.L., Liu J., Ni J., Zhang Y., Lv L.L., Tang R.N., Ni H.F., Ruan X.Z., Liu B.C. (2013) Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition. Int. J. Med. Sci. 10(4), 420.
  59. Maleszewska M., Moonen J.R.A., Huijkman N., van de Sluis B., Krenning G., Harmsen M.C. (2013) IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NF-κB-dependent manner. Immunobiology. 218(4), 443‒454.
  60. Ranchoux B., Tanguay V.F., Perros F. (2020) Endothelial-to-mesenchymal transition in pulmonary hypertension. In: Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension. Eds Nakanishi T., Baldwin H. S., Fineman J.R., Yamagishi H. Singapur: Springer, 63‒70.
  61. Pelouch V., Dixon I., Golfman L., Beamish R.E., Dhalla N.S. (1993) Role of extracellular matrix proteins in heart function. Mol. Cell. Biochem. 129(2), 101‒120.
  62. van Wamel A.J., Ruwhof C., van der Valk-Kokshoorn L.J., Schrier P.I., van der Laarse A. (2002) Stretch-induced paracrine hypertrophic stimuli increase TGF-β1 expression in cardiomyocytes. Mol. Cell. Biochem. 236(1), 147‒153.
  63. Al Hattab D., Czubryt M.P. (2017) A primer on current progress in cardiac fibrosis. Canadian J. Physiol. Pharmacol. 95(10), 1091‒1099.
  64. Ho Y.Y., Lagares D., Tager A.M., Kapoor M. (2014) Fibrosis – a lethal component of systemic sclerosis. Nat. Rev. Rheumatol. 10(7), 390‒402.
  65. Калинин Р.Е., Сучков И.А., Мжаванадзе Н.Д., Короткова Н.В., Климентова Э.А., Поваров В.О. (2021) Метаболиты оксида азота при развитии осложнений после открытых реконструктивных вмешательств у пациентов с периферическим атеросклерозом. Наука молодых – Eruditio Juvenium. 9(3), 407‒414.
  66. Lee E.S., Boldo L.S., Fernandez B.O., Feelisch M., Harmsen M.C. (2017) Suppression of TAK1 pathway by shear stress counteracts the inflammatory endothelial cell phenotype induced by oxidative stress and TGF-β1. Sci. Rep. 7(1), 1‒14.
  67. Jobling M.F., Mott J.D., Finnegan M.T., Jurukovski V., Erickson A.C., Walian P.J., Taylor S.E., Ledbetter S., Lawrense C.M., Rifkin D.B., Barcellos-Hoff M.H. (2006) Isoform-specific activation of latent transforming growth factor β (LTGF-β) by reactive oxygen species. Radiation Res. 166(6), 839‒848.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2.

Baixar (283KB)
Metadados

Declaração de direitos autorais © Е.А. Стрельникова, Р.Е. Калинин, И.А. Сучков, Н.В. Короткова, Н.Д. Мжаванадзе, 2023

Este site utiliza cookies

Ao continuar usando nosso site, você concorda com o procedimento de cookies que mantêm o site funcionando normalmente.

Informação sobre cookies