Arterial hypertension as a consequence of endothelial glycocalyx dysfunction: a modern view of the problem of cardiovascular diseases
https://doi.org/10.15829/1728-8800-2022-3316
Abstract
Arterial hypertension (AH) is a leading risk factor for the development of cardiovascular, cerebrovascular, and renal diseases, which are among the top 10 most common causes of death in the world. The etiology of hypertension has not been fully elucidated, but it has been established that endothelial dysfunction is the most significant pathogenetic link in the formation and progression of the disease. The data obtained in the last 10-15 years on endothelial glycocalyx (eGC) studies indicate that endothelial dysfunction is preceded
by destabilization and shedding of eGC with the appearance of its soluble components in the blood, which is equivalent to a process that can be designated as eGC dysfunction. Signs of eGC dysfunction are expressed in the development of hypertension, diseases of the cardiovascular system, and their complications. The purpose of this review is to analyze and substantiate the pathophysiological role of eGC dysfunction in hypertension and cardiovascular diseases and to describe approaches for its assessment and pharmacological correction. Abstracts and full-size articles of 425 publications in Pubmed/MEDLINE databases over 20 years were studied. The review discusses the role of eGC in the regulation of vascular tone, endothelial barrier function, and anti-adhesive properties of eGC. Modifications of eGC under the influence of pro-inflammatory stimuli, changes in eGC with age, and with increased salt load are considered. The aspect associated with eGC dysfunction in atherosclerosis, hyperglycemia and hypertension is covered. Assessment of eGC dysfunction is difficult but can be performed by indirect methods, in particular by detecting eGC components in blood. A brief description of the main approaches to pharmacoprevention and pharmacocorrection of hypertension is given from the position of exposure effects on eGC, which currently has more a fundamental than practical orientation. This opens up great opportunities for clinical studies of eGC dysfunction for the prevention and treatment of hypertension and justifies a new direction in the clinical pharmacology of antihypertensive drugs.
Keywords
About the Authors
M. M. ZiganshinaRussian Federation
Moscow
A. R. Ziganshin
Russian Federation
Moscow
E. O. Khalturina
Russian Federation
Moscow
I. I. Baranov
Russian Federation
Moscow
References
1. Kobalava ZhD, Konradi AO, Nedogoda SV, et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):3786. (In Russ.) doi:10.15829/1560-4071-2020-3-3786.
2. Barsukov AV, Talantseva MS, Korovin AE, et al. Essential hypertension and inflammation. Bull Russ Military Med Academy. 2013;44(4):229-36. (In Russ.)
3. Shishkin AN, Lyndina ML. Endothelial dysfunction and hypertension. Arterial’naya Gipertenziya (Arterial hypertension). 2008;14(4):315-9. (In Russ.) doi:10.18705/1607-419X-2008-14-4-315-319.
4. Kolářová H, Ambrůzová B, Svihálková Šindlerová L, et al. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediat Inflamm. 2014;2014:694312. doi:10.1155/2014/694312.
5. Maksimenko AV, Turashev AD. Endothelial glycocalyx of blood circulation system. I. Detection, components, and structural organization. Russ J Bioorg Chem. 2014;40(2):119-28. (In Russ.) doi:10.7868/S0132342314020110.
6. Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345-59. doi:10.1007/s00424-007-0212-8.
7. Spiess BD. Heparin: Effects upon the Glycocalyx and Endothelial Cells. J Extra Corpor Technol. 2017;49(3):192-97.
8. Ziganshina MM, Yarotskaya EL, Sukhikh GT, et al. Endothelial Dysfunction as a Consequence of Endothelial Glycocalyx Damage: A Role in the Pathogenesis of Preeclampsia. In: Lenasi H, ed. Endothelial Dysfunction — Old Concepts and New Challenges. IntechOpen, London. 2018. doi:10.5772/intechopen.75043.
9. Iwabuchi K, Nakayama H, Oizumi A, et al. Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans. Mediat Inflamm. 2015;2015:120748. doi:10.1155/2015/120748.
10. Ziganshina MM, Pavlovich SV, Bovin NV, et al. Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia. Acta Naturae. 2016;8(3):59-71. (In Russ.)
11. Tarbel JM, Cancel LM. The glycocalyx and its significance in human medicine. J Intern Med. 2016;280(1):97-113. doi:10.1111/ joim.12465.
12. Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012;40(4):840-8. doi:10.1007/s10439-011-0427-x.
13. Maksimenko AV, Turashev AD, Fedorovich AA, et al. Rat endothelial glycocalyx participates in microcirculatory disorders. Ateroskleroz i Dislipidemii. 2011;3(4):13-29. (In Russ.)
14. Maksimenko AV. Endothelial glycocalyx is significant constitutive part of double protective layer into vascular wall: diagnostic index and therapeutic target. Kardiologicheskij Vestnik. 2016;11(3): 94-100. (In Russ.)
15. Machin DR, Phuong TT, Donato AJ. The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Curr Opin Pharmacol. 2019;45:66-71. doi:10.1016/j.coph.2019.04.011.
16. Ebong EE, Lopez-Quintero SV, Rizzo V, et al. Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1. Integr Biol. 2014;6(3):338-47. doi:10.1039/c3ib40199e.
17. Yen W, Cai B, Yang J, et al. Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo. PLoS One. 2015;10(1):e0117133. doi:10.1371/journal.pone.0117133.
18. Bartosch AMW, Mathews R, Mahmoud MM, et al. Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production. Sci Rep. 2021;11(1):11386. doi:10.1038/s41598-021-90941-w.
19. Melkumyants AM, Balashov SA, Gonchar IV. The influence of the endothelial glycocalyx on the ability of arteries to control their lumen by blood flow rate. Neurosci Behav Physiol. 2017;103(12):1370-6. (In Russ.) М
20. Weinbaum S, Cancel LM, Fu BM, et al. The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases. Cardiovasc Eng Technol. 2021;12(1):37-71. doi:10.1007/s13239020-00485-9.
21. Fleming I, Fisslthaler B, Dixit M, et al. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J. Cell Sci. 2005;118(18):4103-11. doi:10.1242/jcs.02541.
22. Xu S, Ha CH, Wang W, et al. PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling. Cell Signal. 2016;28(3):117-24. doi:10.1016/j.cellsig.2015.12.007.
23. Russell-Puleri S, Dela Paz NG, Adams D, et al. Fluid shear stress induces upregulation of COX-2 and PGI(2) release in endothelial cells via a pathway involving PECAM-1, PI3K, FAK, and p38. Am. J. Physiol. Heart Circ. Physiol. 2017;312(3):H485-500. doi:10.1152/ ajpheart.00035.2016.
24. Sokolov IL, Melkumyants AM, Antonova OA. Endothelial glycocalyx participates in suppression of angiotensin-converting enzyme activity caused by shear stress. Neurosci Behav Physiol. 2019;105(2):198-206. (In Russ.) doi:10.1134/S0869813919020079.
25. Ivanov AN, Puchinyan DM, Norkin IA. Vascular endothelial barrier function. Usp Fiziol Nauk. 2015;46(2):72-96. (In Russ.)
26. Liu X, Fan Y, Deng X. Effect of the endothelial glycocalyx layer on arterial LDL transport under normal and high pressure. J Theor Biol. 2011;283(1):71-81. doi:10.1016/j.jtbi.2011.05.030.
27. Bar A, Targosz-Korecka M, Suraj J, et al. Degradation of Glycocalyx and Multiple Manifestations of Endothelial Dysfunction Coincide in the Early Phase of Endothelial Dysfunction Before Atherosclerotic Plaque Development in Apolipoprotein E/LowDensity Lipoprotein Receptor-Deficient Mice. J Am Heart Assoc. 201919;8(6):e011171. doi:10.1161/JAHA.118.011171.
28. McDonald KK, Cooper S, Danielzak L, et al. Glycocalyx Degradation Induces a Proinflammatory Phenotype and Increased Leukocyte Adhesion in Cultured Endothelial Cells under Flow. PLoS One. 2016;11(12):e0167576. doi:10.1371/journal.pone.0167576.
29. Rodrigues SF, Granger DN. Blood cells and endothelial barrier function. Tissue Barriers. 2015;3(1-2):e978720. doi:10.4161/21688370.2014.978720.
30. Scott DW, Patel RP. Endothelial heterogeneity and adhesion molecules N-glycosylation: implications in leukocyte trafficking in inflammation. Glycobiology. 2013;23(6):622-33. doi:10.1093/glycob/cwt014.
31. Maruhashi T, Soga J, Fujimura N, et al. Endothelial dysfunction, increased arterial stiffness, and cardiovascular risk prediction in patients with coronary artery disease: FMD-J (Flow-Mediated Dilation Japan) Study A. J A. Heart Assoc. 2018;7(14):e008588. doi:10.1161/JAHA.118.008588.
32. Mahmoud M, Mayer M, Cancel LM, et al. The Glycocalyx core protein Glypican 1 protects vessel wall endothelial cells from stiffness-mediated dysfunction and disease. Cardiovasc. Res. 2021;117(6):1592-605. doi:10.1093/cvr/cvaa201.
33. Oberleithner H, Wilhelmi M. Vascular glycocalyx sodium store — determinant of salt sensitivity? Blood Purif. 2015;39(1-3):7-10. doi:10.1159/000368922.
34. Cao RN, Tang L, Xia ZY, et al. Endothelial glycocalyx as a potential theriapeutic target in organ injuries. Chin Med J. 2019;132(8):963-75. doi:10.1097/CM9.0000000000000177.
35. Ostroumova OD, Goloborodova IV, Fomina VM. Cardiovascular risks in type 2 diabetes patients. Cardiovascular Therapy and Prevention. 2018;17(4):81-94. (In Russ.) doi:10.15829/17288800-2018-4-81-94.
36. Nieuwdorp M, van Haeften TW, Gouverneur MCL, et al. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation ac-tivation in vivo. Diabetes. 2006;55(2):480-6. doi:10.2337/diabetes.55.02.06.db05-1103.
37. Nieuwdorp M, Mooij HL, Kroon J, et al. Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes. 2006;55(4):1127-32. doi:10.2337/diabetes.55.04.06.db05-1619.
38. Broekhuizen LN, Lemkes BA, Mooij HL, et al. Effect of sulodexide on endothelial glycocalyx and vascular permeabilityin patients with type 2 diabetes mellitus. Diabetologia. 2010;53(12):2646-55. doi:10.1007/s00125-010-1910-x.
39. Dogne S, Flamion B, Caron N. Endothelial glycocalyx as a shield against diabetic vascular complications: involvement of hyaluronan and hyaluronidases. Arterioscler Thromb Vasc Biol. 2018;38(7):1427-39. doi:10.1161/ATVBAHA.118.310839.
40. Yilmaz O, Afsar B, Ortiz A, et al. The role of endothelial glycocalyx in health and disease. Clin Kidney J. 2019;12(5):611-9. doi:10.1093/ckj/sfz042.
41. van den Berg BM, Spaan JA, Vink H. Impaired glycocalyx barrier properties contribute to enhanced intimal low-density lipoprotein accumulation at the carotid artery bifurcation in mice. Pflugers Arch. 2009;457(6):1199-206. doi:10.1007/s00424-008-0590-6.
42. Cancel LM, Ebong EE, Mensah S, et al. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis. 2016;252:136-46. doi:10.1016/j.atherosclerosis.2016.07.930.
43. Nagy N, Freudenberger T, Melchior-Becker A, et al. Inhibition of hyaluronan synthesis accelerates murine atherosclerosis: novel insights into the role of hyaluronan synthesis. Circulation. 2010;122(22):2313-22. doi:10.1161/CIRCULATIONAHA.110.972653.
44. Ueno M, Sakamoto H, Liao YJ, et al. Blood-brain barrier disruption in the hypothalamus of young adult spontaneously hypertensive rats. Histochem Cell Biol. 2004;122(2):131-7. doi:10.1007/s00418-004-0684-y.
45. Pot C, Chen AY, Ha JN, et al. Proteolytic cleavage of the red blood cell glycocalyx in a genetic form of hypertension. Cell Mol Bioeng. 2011;4(4):678-92. doi:10.1007/s12195-011-0180-0.
46. Ikonomidis I, Voumvourakis A, Makavos G, et al. Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives. J Clin Hypertens. 2018;20(4):672-9. doi:10.1111/jch.13236.
47. Weissgerber TL, Garcia-Valencia O, Milic NM, et al. Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion. J Am Heart Assoc. 2019;8(4):e010647. doi:10.1161/JAHA.118.010647.
48. Berg S, Engman A, Holmgren S, et al. Increased plasma hyaluronan in severe pre-eclampsia and eclampsia. Scand J Clin Lab Invest. 2001;61(2):131-7. doi:10.1080/00365510151097647.
49. Hentschke MR, Lucas LS, Mistry HD, et al. Endocan-1 concentrations in maternal and fetal plasma and placentae in pre-eclampsia in the third trimester of pregnancy. Cytokine. 2015;74(1):152-6. doi:10.1016/j.cyto.2015.04.013.
50. Siddiqui MF, Nandi P, Girish GV, et al. Decorin over-expression by decidual cells in preeclampsia: a potential blood biomarker.Am J Obstet Gynecol. 2016;215(3):361.e1-361.e15. doi:10.1016/j.ajog.2016.03.020.
51. Gouverneur M, Berg B, Nieuwdorp M, et al. Vasculoprotective properties of the endothelial glycocalyx: effects of fluid shear stress. J Intern Med. 2006;259(4):393-400. doi:10.1111/j.13652796.2006.01625.x.
52. Ziganshina MM, Yarotskaya EL, Bovin NV, et al. Can Endothelial Glycocalyx Be a Major Morphological Substrate in PreEclampsia? Int J Mol Sci. 2020;21(9):3048. doi:10.3390/ijms21093048.
53. Kang H, Deng X. The Endothelial Glycocalyx: Visualization and Measurement. J Biomed 2017;2:120-3. doi:10.7150/jbm.20986.
54. Nieuwdorp M, Meuwese MC, Mooij HL, et al. Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability. J Appl Physiol. 2008;104(3):84552. doi:10.1152/japplphysiol.00440.2007.
55. Lekakis J, Abraham P, Balbarini A, et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil. 2011;18(6):775-89. doi:10.1177/1741826711398179.
56. Gorshkov AYu, Gumanova NG, Boytsov SA. Potential marker of endothelial dysfunction in patients with various grade of cardiovascular risk. Cardiovascular Therapy and Prevention. 2016;15(2):57-62. (In Russ.) doi:10.15829/1728-8800-2016-2-57-62.
57. Vlasov TD, Lazovskaya OA, Shimanski DA, et al. The endothelial glycocalyx: research methods and prospects for their use in endothelial dysfunction assessment. Regionarnoe krovoobraŝenie i mikrocirkulâciâ 2020;19(73):5-16. (In Russ.) doi:10.24884/1682-6655-2020-19-1-5-16.
58. Ziganshina MM, Pavlovich SV. New approaches to the prevention and treatment of arterial hypertension from the standpoint of pharmacological correction of endothelial glycocalyx: experimental and clinical data. Eksp Klin Farmakol. 2021;84(7):26-36. (In Russ.doi:10.30906/0869-2092-2021-84-7-26-36.
59. Gorshkov AYu, Boytsov SA. Endothelial glycocalyx — potential vascular biomarker: diagnostic and therapeutic target in cardiovascular diseases. Cardiovascular Therapy and Prevention. 2015;14(6):87-92. (In Russ.) doi:10.15829/1728-8800-2015-6-87-92.
60. Sokologorsii SV, Ovechkin AM, Politov ME, Bulanova EL. To restore a glycocalyx! Is there any opportunities? Russ J Anаеsth Reanim. 2022;1:102-10. (In Russ.) doi:10.17116/anaesthesiology2022011102.
Supplementary files
Review
For citations:
Ziganshina M.M., Ziganshin A.R., Khalturina E.O., Baranov I.I. Arterial hypertension as a consequence of endothelial glycocalyx dysfunction: a modern view of the problem of cardiovascular diseases. Cardiovascular Therapy and Prevention. 2022;21(9):3316. (In Russ.) https://doi.org/10.15829/1728-8800-2022-3316