Endothelial dysfunction. Do we understand this term properly?
https://doi.org/10.21292/2078-5658-2020-17-2-76-84
Abstract
The objective: to clarify the limits of using the term of endothelial dysfunction in research and clinical work.
Results: the concept of endothelial dysfunction has become ingrained in research activities while in clinical work, it is used rarely and fairly often inadequately. It is recommended that endothelial dysfunction should be understood as a persistent change in the structure and/or functional activity of endothelium resulting in vascular tone disorders, thrombosis and other complications. The concept of "dysfunction" and "activation" of epithelium should be differentiated. One means the injury, the other reflects changes in response to various provocative effects. The markers of endothelial dysfunction (instrumental and biochemical) and ways of its management with certain pharmacological agents (antioxidants, NADP-oxydases inhibitors, etc.) have been discussed.
About the Authors
T. D. Vlasov
Pavlov First Saint Petersburg State Medical University
Russian Federation
Russian Federation
Timur D. Vlasov - Head of Morbid Physiology Department with Training in Clinical Morbid Physiology,
Director of Academic Institute for Biomedicine
6-8, Lva Tolstogo St., St. Petersburg, 197022
N. N. Petrischev
Pavlov First Saint Petersburg State Medical University
Russian Federation
Russian Federation
Nikolay N. Petrischev - Professor of Morbid Physiology Department with Training in Clinical Morbid Physiology, Director of Laser Medicine Department
6-8, Lva Tolstogo St., St. Petersburg, 197022
O. A. Lazovskaya
Pavlov First Saint Petersburg State Medical University
Russian Federation
Russian Federation
Olga A. Lazovskaya - Assistant Department for General Practice of Family Medicine
6-8, Lva Tolstogo St., St. Petersburg, 197022
References
1. Vasina L V., Vlasov T.D., Petrischev N.N. Functional heterogeneity of endothelium (review). Аrterialnaya Gipertenziya, 2017, vol. 23, no. 2, pp. 88-102. (In Russ.)
2. Kudlay D.А. Immunometabolicheskie aspekty patogeneza politravmy. Avtoref. dokt. med. nauk. [Immonumetabolic aspects of pathogenesis of multiple trauma. Doct. Diss.]. Novosibirsk State Medical University of the Russian Federal Agency on Healthcare and Social Development, Novosibirsk, 2007.
3. Petrischev N.N., Vasina L.V., Vlasov T.D. et al. Typical forms of endothelial dysfunction. Kliniko-laboratorny Konsilium, 2007, no. 18, pp. 31‒35.(In Russ.)
4. Tsybikov N.N., Fefelova E.V., Tereshkov P.P. et al. Endothelial dysfunction with experimental hyperhomocytheinemia. Patologicheskaya Fiziologiya i Eksperimentalnaya Terapiya, 2016, vol. 60, no. 3, pp. 42-46. (In Russ.)
5. Abrahamson E.E., Ikonomovic M.D. Brain injury-induced dysfunction of the blood brain barrier as a risk for dementia. Exp. Neurol., 2020, Feb 21:113257. doi: 10.1016/j.expneurol.2020.113257.
6. Agnihotri N., Mishra P.C. Mechanism of scavenging action of N-Acetylcysteine for the OH radical: A quantum computational study. J. Physical Chemistry B, 2009, vol. 113, no. 35, pp. 12096–12104. https://doi.org/10.1021/jp903604s.
7. Altenhöfer S., Radermacher K.A., Kleikers P.W.M. et al. Evolution of NADPH oxidase inhibitors: Selectivity and mechanisms for target engagement. Antioxidants and Redox Signaling, 2005, vol. 23, no. 5, pp. 406–427. https://doi.org/10.1089/ars.2013.5814
8. Apte R.S., Chen D.S., Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell, 2009, vol. 176, no. 6, pp. 1248–1264. https://doi.org/10.1016/j.cell.2019.01.021.
9. Atasayan K., Yoldemir T., Ramoglu S. et al. The evaluation of endothelial function and structure in hirsute patients in reproductive age. Eur. J. Obstet. Gynecol. Reprod. Biol., 2016, vol. 206, pp. 208‒212. doi: 10.1016/j.ejogrb.2016.09.003. Epub 2016 Oct 3.
10. Augustin H.G., Kozian D.H., Johnson R.C. Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. BioEssays, 1994, vol. 16, no. 12, pp. 901-906.
11. Celermajer D.S., Sorensen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 1992, vol. 340(8828), pp. 1111‒1115.
12. Cines D.B., Pollak E.S., Buck C.A. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood, 1998, vol. 91, no. 10, pp. 3527-3561.
13. Colbert J.F., Schmidt E.P. Endothelial and Microcirculatory Function and Dysfunction in Sepsis. Clin. Chest Med., 2016, vol. 37, no. 2, pp. 263‒275. doi: 10.1016/j.ccm.2016.01.009.
14. Dandona P., Phil D. Insulin resistance and endothelial dysfunction in atherosclerosis: implications and interventions. Diabetes Technology & Therapeutics, 2002, vol. 4, no. 6, pp. 809‒815.
15. De Felice F., Megiorni F., Pietrantoni I. et al. Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program. Eur. Rev. Med. Pharmacol. Sciences, 2009, vol. 23, no. 6, pp. 2669‒2680. https://doi.org/10.26355/eurrev_201903_17415.
16. Deanfield J.E., Halcox J.P., Rabelink T.J. Endothelial function and dysfunction: testing and clinical relevance. Circulation, 2007, vol. 115, no. 10, pp. 1285‒1295.
17. Dilaveris P., Giannopoulos G., Riga M. et al. Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr. Vasc. Pharmacology, 2007, vol. 5, pp. 227–237. https://doi.org/10.2174/157016107781024091.
18. Drummond G.R., Sobey C.G. Endothelial NADPH oxidases: Which NOX to target in vascular disease? Trends in Endocrinology and Metabolism, 2014, vol. 25, no. 9, pp. 452–463. https://doi.org/10.1016/j.tem.2014.06.012.
19. Elbini Dhouib I., Jallouli M., Annabi A. et al. A minireview on N-acetylcysteine: An old drug with new approaches. Life Sciences, 2016, vol. 151, pp. 359–363. https://doi.org/10.1016/j.lfs.2016.03.003.
20. Furchgott R.F., Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, vol. 288(5789), pp. 373‒376.
21. Furchgott R.F., Cherry P.D., Zawadzki J.V., Jothianandan D. Endothelial cells as mediators of vasodilation of arteries. J. Cardiovasc. Pharmacol., 1984, vol. 6, suppl. 2, pp. S336-S343.
22. Hermida N., Balligand J.L. Low-density lipoprotein-cholesterol-induced endothelial dysfunction and oxidative stress: The role of statins. Antioxidants and Redox Signaling, 2014, vol. 20, no. 8, pp. 1216–1237. https://doi.org/10.1089/ars.2013.5537.
23. Imanishi T., Ikejima H., Tsujioka H. et al. Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Hypertension, 2008, vol. 51, no. 3, pp. 734–741. https://doi.org/10.1161/HYPERTENSIONAHA.107.104299.
24. Jelić-Knezović N., Galijašević S., Lovrić M. et al. Levels of nitric oxide metabolites and myeloperoxidase in subjects with type 2 diabetes mellitus on metformin therapy. Exp. Clin. Endocrinol. Diabetes, 2019, vol. 127, no. 1, pp. 56‒61. doi: 10.1055/a-0577-7776.
25. Kershaw K.N., Lane-Cordova A.D., Carnethon M.R. et al. Chronic stress and endothelial dysfunction: the multi-ethnic study of atherosclerosis (MESA). Am. J. Hypertens., 2017, vol. 30, no. 1, pp. 75‒80.
26. Konukoglu D., Uzun H. Endothelial Dysfunction and Hypertension. Adv. Exp. Med. Biol., 2017, vol. 956, pp. 511‒540. doi: 10.1007/5584_2016_90.
27. Kurutas E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutrition J., 2016, vol. 15, no. 1, pp. 71. https://doi.org/10.1186/s12937-016-0186-5.
28. Leligdowicz A., Richard-Greenblatt M., Wright J. et al. Endothelial activation: the ang/tie axis in sepsis. Front Immunol., 2018, vol. 9, pp. 838. doi: 10.3389/fimmu.2018.00838.
29. Liu C., Chen J. Endothelin receptor antagonists for pulmonary arterial hypertension. In Chao Liu (Ed.), 2004, Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. https://doi.org/10.1002/14651858.CD004434.pub2.
30. Mandosi E., Giannetta E., Filardi T. et al. Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes. Expert Opinion on Therapeutic Targets, 2015, vol. 19, no. 12, pp. 1617–1622. https://doi.org/10.1517/14728222.2015.1066337.
31. Melnikov I.S., Kozlov S.G., Saburova O.S. et al. Current position on the role of monomeric C-reactive protein in vascular pathology and atherothrombosis. Curr. Pharm. Res., 2019, vol. 16. doi: 10.2174/1381612825666191216144055.
32. Murdaca G., Spanò F., Cagnati P. et al. Free radicals and endothelial dysfunction: potential positive effects of TNF-α inhibitors. Redox. Rep., 2013, vol. 18, no. 3, pp. 95‒99. doi: 10.1179/1351000213Y.0000000046.
33. Nafisa A., Gray S.G., Cao Y. et al. Endothelial function and dysfunction: Impact of metformin. Pharmacology and Therapeutics, 2018, vol. 192, pp. 150–162. https://doi.org/10.1016/j.pharmthera.2018.07.007.
34. Oelze M., Daiber A., Brandes R.P. et al. Nebivolol inhibits superoxide formation by NADPH oxidase and endothelial dysfunction in angiotensin II-treated rats. Hypertension, 2006, vol. 48, no. 4, pp. 677–684. https://doi.org/10.1161/01.HYP.0000239207.82326.29.
35. Oikonomou E., Siasos G., Tsigkou V. et al. Coronary artery disease and endothelial dysfunction: Novel diagnostic and therapeutic approaches. Curr. Med. Chem., 2019, vol. 144, no. 3, pp. 253‒267. doi: 10.2174/0929867326666190830103219.
36. Peller M., Ozierański K., Balsam P. et al. Influence of beta-blockers on endothelial function: A meta-analysis of randomized controlled trials. Cardiol. J., 2015, vol. 22, no. 6, pp. 708–716. https://doi.org/10.5603/CJ.a2015.0042.
37. Rafnsson A., Shemyakin A., Pernow J. Selective endothelin ETA and dual ETA/ETB receptor blockade improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease. Life Sciences, 2014, vol. 118, no. 2, pp. 435–439. https://doi.org/10.1016/j.lfs.2014.02.026.
38. Reis J., Massari M., Marchese S. et al. A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action. Redox Biology, 2020, vol. 32, 101466. https://doi.org/10.1016/j.redox.2020.101466.
39. Shao D., Park J.E.S., Wort S.J. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacological Research, 2011, vol. 63, no. 6, pp. 504–511. https://doi.org/10.1016/j.phrs.2011.03.003.
40. Silva I.V.G., De Figueiredo, R.C., Rios D.R.A. Effect of different classes of antihypertensive drugs on endothelial function and inflammation. Intern. J. Molecul. Sci., 2019, vol. 20, no. 14. https://doi.org/10.3390/ijms20143458.
41. Sosińska P., Baum E., Maćkowiak B. et al. Sulodexide Reduces the proinflammatory effect of serum from patients with peripheral artery disease in human arterial endothelial cells. Cellular Physiol. Biochem., 2016, vol. 40, no. 5, pp. 1005–1012. https://doi.org/10.1159/000453157.
42. Stojanović M., Prostran M., Radenković M. Thiazolidinediones improve flow-mediated dilation: a meta-analysis of randomized clinical trials. Eur. J. Clin. Pharmacology, 2016, vol. 72, no. 4, pp. 385–398. https://doi.org/10.1007/s00228-015-1999-4.
43. Su J.B. Vascular endothelial dysfunction and pharmacological treatment. World J. Cardiology, 2015, vol. 7, no. 11, pp. 719. https://doi.org/10.4330/wjc.v7.i11.719.
44. Targonski P.V., Bonetti P.O., Pumper G.M. et al. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation, 2003, vol. 107, no. 22, pp. 2805‒2809.
45. Vetter M.W., Martin B.J., Fung M. et al. Microvascular dysfunction in schizophrenia: a case-control study. NPJ Schizophr., 2015, vol. 1:15023. doi: 10.1038/npjschz.2015.23.
46. Whitt M.D., Jackson M.J. Practicality and importance of selected endothelial dysfunction measurement techniques: review. Biomed. Eng. Lett., 2018, vol. 9, no. 1, pp. 87‒95. doi: 10.1007/s13534-018-0089-9.
Review
For citations:
Vlasov T.D., Petrischev N.N., Lazovskaya O.A. Endothelial dysfunction. Do we understand this term properly? Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2020;17(2):76-84. (In Russ.) https://doi.org/10.21292/2078-5658-2020-17-2-76-84
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