The concept of endothelial transcytosis as a theoretical prerequisite for the development of prevention and treatment of atherosclerosis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Understanding how focal atherosclerotic lesions are formed in the vascular wall currently remains clearly incomplete, and primarily because the discussion of this issue is usually considered at the stage when low-density lipoproteins are already in the intima; the situation is largely clarified if attention is paid primarily to the mechanisms of intima infiltration by lipoproteins. From the modern point of view, we are talking about the molecular mechanisms of transcytosis, previously detected by the electron microscopy on endothelial cells of rat capillaries, which were injected with gold or ferritin nanoparticles to trace their path in the cytoplasm. Transcytosis as an active process, in which a number of receptors are involved, is contrasted with passive lipoproteins infiltration of the vascular wall. In addition to these concepts, the review discusses possible conditions for the implementation of low-density lipoproteins transcytosis, as well as the issues of regulation of transcytosis.

About the authors

Nina S. Parfenova

Institute of Experimental Medicine

Author for correspondence.
Email: nina.parf@mail.ru
SPIN-code: 9415-0241

MD, Cand. Sci. (Med.), Senior Research Associate, Department of Biochemistry

Russian Federation, Санкт-Петербург

Dmitry A. Tanyanskiy

Institute of Experimental Medicine

Email: dmitry.athero@gmail.com
ORCID iD: 0000-0002-5321-8834
SPIN-code: 9303-9445
Scopus Author ID: 53878682400
ResearcherId: G-3307-2015

MD, Dr. Sci. (Med.), Head of Department of Biochemistry

Russian Federation, Saint Petersburg

References

  1. Anitschkow N. Über experimentelle Cholesterinsteatose und ihre Bedeutung für die Entstehung einiger pathologischen Prozesse. Zbl Allg Path Path Anat. 1913;24(1):1–9. (In German)
  2. Grotte G. Passage of dextran molecules across the blood-lymph barrier. Acta Chir Scand Suppl. 1956;211:1–84.
  3. Michel CC, Nanjee MN, Olszewski WL, Miller NE. LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans. J Lipid Res. 2015;56(1):122–128. doi: 10.1194/jlr.M055053
  4. Stender S, Zilversmit DB. Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx. Arteriosclerosis. 1981;1(1):38–49. doi: 10.1161/01.atv.1.1.38
  5. Palade GE, Bruns RR. Structural modulations of plasmalemmal vesicles. J Cell Biol. 1968;37(3):633–649. doi: 10.1083/jcb.37.3.633
  6. Bruns RR, Palade GE. Studies on blood capillaries. II. Transport of ferritin molecules across the wall of muscle capillaries. J Cell Biol. 1968;37(2):277–299. doi: 10.1083/jcb.37.2.277
  7. Snelting-Havinga I, Mommaas M, van Hinsbergh VW, et al. Immunoelectron microscopic visualization of the transcytosis of low-density lipoproteins in perfused rat arteries. Eur J Cell Biol. 1989;48(1):27–36.
  8. Jang E, Robert J, Rohrer L, et al. Transendothelial transport of lipoproteins. Atherosclerosis. 2020;315:111–125. DOI: 10.1016/ j.atherosclerosis.2020.09.020
  9. Schnitzer JE, Allard J, Oh P. NEM inhibits transcytosis, endocytosis, and capillary permeability: implication of caveolae fusion in endothelia. Am J Physiol. 1995;268(1 Pt 2):H48–55. doi: 10.1152/ajpheart.1995.268.1.H48
  10. Frank PG, Pavlides S, Cheung MW, et al. Role of caveolin-1 in the regulation of lipoprotein metabolism. Am J Physiol Cell Physiol. 2008;295(1):242–248. doi: 10.1152/ajpcell.00185.2008
  11. Frank PG, Lee H, Park DS, et al. Genetic ablation of caveolin-1 confers protection against atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24(1):98–105. doi: 10.1161/01.ATV.0000101182.89118.E5
  12. Fernández-Hernando C, Yu J, Suárez Y, et al. Genetic evidence supporting a critical role of endothelial caveolin-1 during the progression of atherosclerosis. Cell Metab. 2009;10(1):48–54. doi: 10.1016/j.cmet.2009.06.003
  13. Armstrong SM, Sugiyama MG, Fung KY, et al. A novel assay uncovers an unexpected role for SR-BI in LDL transcytosis. Cardiovasc Res. 2015;108(2):268–277. doi: 10.1093/cvr/cvv218
  14. Rohrer L, Ohnsorg PM, Lehner M, et al. High-density lipoprotein transport through aortic endothelial cells involves scavenger receptor BI and ATP-binding cassette transporter G1. Circ Res. 2009;104(10):1142–1150. doi: 10.1161/CIRCRESAHA.108.190587
  15. Fung KY, Wang C, Nyegaard S, et al. SR-BI mediated transcytosis of HDL in brain microvascular endothelial cells is independent of caveolin, clathrin, and PDZK1. Front Physiol. 2017;8:1–16. doi: 10.3389/fphys.2017.00841
  16. Lim HY, Thiam CH, Yeo KP, et al. Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-Mediated transport of HDL. Cell Metab. 2013;17(5):671–684. doi: 10.1016/j.cmet.2013.04.002
  17. Schubert W, Frank PG, Woodman SE, et al. Microvascular hyperpermeability in caveolin-1 (-/-) knockout mice. J Biol Chem. 2002;277(42):40091–40098. doi: 10.1074/jbc.M205948200
  18. Goldberg D, Khatib S. Atherogenesis, Transcytosis, and the Transmural Cholesterol Flux: A Critical Review. Oxid Med Cell Longev. 2022;2022:2253478. doi: 10.1155/2022/2253478
  19. Dehouck B, Fenart L, Dehouck MP, et al. A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier. J Cell Biol. 1997;138(4):877–889. doi: 10.1083/jcb.138.4.877
  20. Zakharova FM, Damgaard D, Mandelshtam MY, et al. Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia. BMC Med Genet. 2005;6:6. doi: 10.1186/1471-2350-6-6
  21. Kraehling JR, Chidlow JH, Rajagopal C, et al. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells. Nat Commun. 2016;7:1–15. doi: 10.1038/ncomms13516
  22. Tao B, Kraehling JR, Ghaffari S, et al. BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells. J Biol Chem. 2020;295(52):18179–18188. doi: 10.1074/jbc.RA120.015680
  23. Tan JT, Prosser HC, Dunn LL, et al. High-density lipoproteins rescue diabetes-impaired angiogenesis via scavenger receptor Class B Type I. Dibetes. 2016;65(10):3091–3103. doi: 10.2337/db15-1668
  24. Zhu W, Saddar S, Seetharam D, et al. PDZK1 maintains endothelial monolayer integrity. Сirc Res. 2008;102(4):480–487. doi: 10.1161/CIRCRESAHA.107.159079
  25. Kimura T, Tomura H, Mogi C, et al. Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells. J Biol Chem. 2006;281(49):37457–37467. doi: 10.1074/jbc.M605823200
  26. Lu SM, Fairn GD. Mesoscale organization of domains in the plasma membrane – beyond the lipid raft. Crit Rev Biochem Mol Biol. 2018;53(2):192–207. doi: 10.1080/10409238.2018.1436515
  27. Wang DX, Pan YQ, Liu B, Dai L. Cav-1 promotes atherosclerosis by activating JNK-associated signaling. Biochem Biophys Res Commun. 2018;503(2):513–520. doi: 10.1016/j.bbrc.2018.05.036
  28. Fernández-Hernando C, Yu J, Dávalos A, et al. Endothelial-specific overexpression of caveolin-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol. 2010;177(2):998–1003. doi: 10.2353/ajpath.2010.091287
  29. Ramírez CM, Zhang X, Bandyopadhyay C, et al. Caveolin-1 regulates atherogenesis by attenuating low density lipoprotein transcytosis and vascular inflammation independently of endothelial nitric oxide synthase activation. Circulation. 2019;140(3):225–239. doi: 10.1161/CIRCULATIONAHA.118.038571
  30. Huang L, Chambliss KL, Gao X, et al. SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature. 2019;569(7757):565–569. doi: 10.1038/s41586-019-1140-4
  31. Armstrong SM, Khajoee V, Wang C, et al. Co-regulation of transcellular and paracellular leak across microvascular endothelium by dynamin and Rac. Am J Pathol. 2012;180(3):1308–1323. doi: 10.1016/j.ajpath.2011.12.002
  32. Sverdlov M, Shinin V, Place AT, et al. Filamin A regulates caveolae internalization and trafficking in endothelial cells. Mol Biol Cell. 2009;20(21):4531–4540. doi: 10.1091/mbc.e08-10-0997
  33. Tuma PL, Hubbard AL. Transcytosis: crossing cellular barriers. Physiol Rev. 2003;83(3)871–932. doi: 10.1152/physrev.00001.2003
  34. Fung KYY, Fairn GD, Lee WL. Transcellular vesicular transport in epithelial and endothelial cells: challenges and opportunities. Traffic. 2018;19(1):5–18. doi: 10.1111/tra.12533
  35. Villaseñor R, Schilling M, Sundaresan J, et al. Sorting tubules regulate blood-brain barrier transcytosis. Cell Rep. 2017;21(11):3256–3270. doi: 10.1016/j.celrep.2017.11.055
  36. Denisenko AD. Modified lipoproteins and atherosclerosis. In: Aleksandrova GI, Aleshina GM, Burova LA, et al. Institute of experimental medicine on the eve of new millenium. Achievements in the field of experimental biology and medicine. Ed. by B.I. Tkachenko. Saint Petersburg: Nauka; 2000. P. 264–285. (In Russ.)
  37. Schnitzer JE, Liu J, Oh P. Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem. 1995;270(24):14399–14404. doi: 10.1074/jbc.270.24.14399
  38. Predescu SA, Predescu DN, Palade GE. Endothelial transcytotic machinery involves supramolecular protein-lipid complexes. Mol Biol Cell. 2001;12(4):1019–1033. doi: 10.1091/mbc.12.4.1019
  39. Villablanca AC, Jayachandran M, Banka C. Atherosclerosis and sex hormones: current concepts. Clin Sci (Lond). 2010;119(12):493–513. doi: 10.1042/CS20100248
  40. Ghaffari S, Naderi Nabi F, Sugiyama MG, Lee WL. Estrogen inhibits LDL (low density lipoprotein) transcytosis by human coronary artery endothelial cells via GPER (G-protein-coupled estrogen receptor) and SR-BI (scavenger receptor class B type 1). Arterioscler Thromb Vasc Biol. 2018;38(10):2283–2294. doi: 10.1161/ATVBAHA.118.310792
  41. Bobryshev YuV, Nagornev VA, Klimov AN. Stereological analysis of nonspecific endocytic capture of lipoproteins by the aortic endothelium in the initial stages of experimental atherosclerosis in rabbits. Arch Pathol. 1984;46(10):36–42. (In Russ.)
  42. Bartels ED, Christoffersen C, Lindholm MW, Nielsen LB. Altered metabolism of LDL in the arterial wall precedes atherosclerosis regression. Circ Res. 2015;117(11):933–942. doi: 10.1161/CIRCRESAHA.115.307182
  43. Navab M, Hough GP, Berliner JA, et al. Rabbit beta-migration very low density lipoprotein increases endothelial macromolecular transport without altering electrical resistance. J Clin Invest. 1986;78(2):389–397. doi: 10.1172/JCI112589
  44. Christoffersen C, Nielsen LB. Apolipoprotein M: bridging HDL and endothelial function. Curr Opin Lipidol. 2013;24(4):295–300. doi: 10.1097/MOL.0b013e328361f6ad
  45. Wilkerson BA, Argraves KM. The role of sphingosine-1-phosphate in endothelial barrier function. Biochim Biophys Acta. 2014;1841(10):1403–1412. doi: 10.1016/j.bbalip.2014.06.012
  46. Feuerborn R, Besser M, Potì F, et al. Elevating endogenous sphingosine-1-phosphate (S1P) levels improves endothelial function and ameliorates atherosclerosis in low density lipoprotein receptor-deficient (LDL-R -/-) mice. Thromb Haemost. 2018;118(8):1470–1480. doi: 10.1055/s-0038-1666870
  47. Velagapudi S, Rohrer L, Poti F, et al. Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein. Arterioscler Thromb Vasc Biol. 2021;41(10):e468–e479. doi: 10.1161/ATVBAHA.121.316725
  48. Kornerup K, Nordestgaard BG, Feldt-Rasmussen B, et al. Transvascular low-density lipoprotein transport in patients with diabetes mellitus (type 2): a noninvasive in vivo isotope technique. Arterioscler Thromb Vasc Biol. 2002;22(7):1168–1174. doi: 10.1161/01.atv.0000022849.26083.fa
  49. Bai X, Yang X, Jia X, et al. CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose stimulated LDL transcytosis. Autophagy. 2020;16(6):1111–1129. doi: 10.1080/15548627.2019.1659613
  50. Zhao Y, Jia X, Yang X, et al. Deacetylation of Caveolin-1 by Sirt6 induces autophagy and retards high glucose-stimulated LDL transcytosis and atherosclerosis formation. Metabolism. 2022;131:155162. doi: 10.1016/j.metabol.2022.155162
  51. Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54(23):2129–2138. doi: 10.1016/j.jacc.2009.09.009
  52. Nazarov PG, Maltseva ON, Tanyansky DA, et al. Influence of inflammatory factors on transendothelial transport of serum lipoproteins in vitro. Cytokines and inflammation. 2015;14(4):59–64. (In Russ.)
  53. Nazarov PG, Maltseva ON, Tanyanskiy DA, et al. Mast Cells and Control of Transendothelial Transport: the Role of Histamine. Cell Tiss Biol. 2021;15:402–408. doi: 10.1134/S1990519X21040052
  54. Zhang Y, Yang X, Bian F, et al. TNF-α promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-κB and PPAR-γ. J Mol Cell Cardiol. 2014;72:85–94. doi: 10.1016/j.yjmcc.2014.02.012
  55. Jia X, Liu Z, Wang Y, et al. Serum amyloid A and interleukin-1β facilitate LDL transcytosis across endothelial cells and atherosclerosis via NF-κB/caveolin-1/cavin-1 pathway. Atherosclerosis. 2023. doi: 10.1016/j.atherosclerosis.2023.03.004. Epub ahead of print.
  56. Kiseleva EP, Krylov AV, Starikova EhA, Kuznetsova SA. Faktor rosta sosudistogo ehndoteliya i immunnaya sistema. Uspekhi sovremennoi biologii. 2009;129(4):336–347. (In Russ.)
  57. Lee YT, Lin HY, Chan YW, et al. Mouse models of atherosclerosis: a historical perspective and recent advances. Lipids Health Dis. 2017;16(1):1–11. doi: 10.1186/s12944-016-0402-5
  58. Zadelaar S, Kleemann R, Verschuren L, et al. Mouse models for atherosclerosis and pharmaceutical modifiers. Arterioscler Thromb Vasc Biol. 2007;27(8):1706–1721. doi: 10.1161/ATVBAHA.107.142570
  59. Daugherty A. Mouse models of atherosclerosis. Am J Med Sci. 2002;323(1):3–10. doi: 10.1097/00000441-200201000-00002
  60. Parfenova NS. The role of endothelium in atherogenesis: dependence of atherosclerosis development on the properties of vessel endothelium. Medical Academic Journal. 2020;20(1):23–36. (In Russ.) doi: 10.17816/MAJ25755

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Typical lesion riched in foam cells in a rabbit fed a total of 82.7 g of pure cholesterol in a sunflower oil over a period of 139 days. Chol.Ph. — large phagocytes loaded with cholesterol; End. — endothelial cells; Plb. — wandering lymphoid cells; Mf. — smooth muscle cells of the aortic wall. [Anitschkow N. Über die Veränderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose. Beitr Pathol Anat. 1913;56:379–404]

Download (254KB)
Indexing metadata
3. Fig. 2. Model of low-density lipoproteins (LDL) transendothelial transport and its regulation. Аctivin-like kinase 1 (ALK-1) and scavenger receptor class B type 1 (SR-B1) bind to LDL, which leads to the internalization of the latter through caveoles. The binding of SR-B1 to LDL induces the association of the guanyl-nucleotide exchange factor DOCK-4 with the cytoplasmic domain of SR-B1, which leads to the activation of GTPase Rac-1 and movement of the F-actin cytoskeleton. Further post-receptor events regulating LDL transcytosis are poorly understood but they likely require Rab and SNARE proteins. Estradiol suppresses LDL transcytosis by interacting with G-protein coupled estrogen receptors, which leads to suppression of SR-B1 synthesis. Tumor necrosis factor (TNF) induces LDL transcytosis by increasing the synthesis of caveolin-1 (Cav-1) through the activation of transcription factors Nf-кB and PPARγ. Glucose in high concentrations also promotes LDL transcytosis by reducing the degradation of Cav-1 in lysosomes through the suppression of nuclear-cytoplasmic translocation of Sirt6 deacetylase; deacetylated Cav-1 (deacet-Cav-1) undergoes autophagy

Download (231KB)
Indexing metadata

Copyright (c) 2023 Eco-Vector



Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».