Skip to main content

Advertisement

Log in

Caveolae and transcytosis in endothelial cells: role in atherosclerosis

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The endothelium plays an important role in the regulation of molecular exchanges between the blood and peripheral tissues. The transport of molecules between tissues must be tightly controlled in order to maintain homeostasis between the different organs of the body. The endothelial transcytosis pathway has been shown to direct the transfer of proteins and solutes and therefore to act as a filtering system. This transport mode has been demonstrated to involve plasma-membrane vesicles that may be transferred with their cargo components from the apical to the basal side of endothelial cells. Among the vesicles implicated in the regulation of transcytosis, caveolae, which are 50 to 100-nm plasma-membrane invaginations, have been reported to play an essential part. In this paper, we review the function of caveolae and their major protein component (i.e., caveolin-1) in the regulation of endothelial transcytosis. The roles of caveolae in vascular diseases, such as atherosclerosis, are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Baker ME (2002) Albumin, steroid hormones and the origin of vertebrates. J Endocrinol 175:121–127

    Article  PubMed  CAS  Google Scholar 

  • Balazs Z, Panzenboeck U, Hammer A, Sovic A, Quehenberger O, Malle E, Sattler W (2004) Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J Neurochem 89:939–950

    Article  PubMed  CAS  Google Scholar 

  • Bouzin C, Feron O (2007) Targeting tumor stroma and exploiting mature tumor vasculature to improve anti-cancer drug delivery. Drug Resist Update 10:109–120

    Article  CAS  Google Scholar 

  • Broadwell RD, Balin BJ, Salcman M (1988) Transcytotic pathway for blood-borne protein through the blood-brain barrier. Proc Natl Acad Sci USA 85:632–636

    Article  PubMed  CAS  Google Scholar 

  • Cameron PL, Ruffin JW, Bollag R, Rasmussen H, Cameron RS (1997) Identification of caveolin and caveolin-related proteins in the brain. J Neurosci 17:9520–9535

    PubMed  CAS  Google Scholar 

  • Chuang VT, Kragh-Hansen U, Otagiri M (2002) Pharmaceutical strategies utilizing recombinant human serum albumin. Pharm Res 19:569–577

    Article  PubMed  Google Scholar 

  • Cohen AW, Park DS, Woodman SE, Williams TM, Chandra C, Shirani J, Pereira De Souza A, Kitsis RN, Russell RG, Weiss LM, Tang B, Jelicks LA, Factor SM, Shtutin V, Tanowitz HB, Lisanti MP (2003) Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol 284:457–474

    Google Scholar 

  • De Vries HE, Kuiper J, De Boer AG, Van Berkel TJC, Breimer DD (1993) Characterization of the scavenger receptor on bovine cerebral endothelial cells in vitro. J Neurochem 61:1813–1821

    Article  PubMed  Google Scholar 

  • Dehouck B, Fenart L, Dehouck MP, Pierce A, Torpier G, Cecchelli R (1997) A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier. J Cell Biol 138:877–889

    Article  PubMed  CAS  Google Scholar 

  • Dolcini L, Caridi G, Dagnino M, Sala A, Gokce S, Sokucu S, Campagnoli M, Galliano M, Minchiotti L (2007) Analbuminemia produced by a novel splicing mutation. Clin Chem 53:1549–1552

    Article  PubMed  CAS  Google Scholar 

  • Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293:2449–2452

    Article  PubMed  CAS  Google Scholar 

  • Esposito C, Gerlach H, Brett J, Stern D, Vlassara H (1989) Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface properties. J Exp Med 170:1387–1407

    Article  PubMed  CAS  Google Scholar 

  • Frank PG, Lisanti MP (2004) Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol 15:523–529

    Article  PubMed  CAS  Google Scholar 

  • Frank PG, Woodman SE, Park DS, Lisanti MP (2003) Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23:1161–1168

    Article  PubMed  CAS  Google Scholar 

  • Frank PG, Lee H, Park DS, Tandon NN, Scherer PE, Lisanti MP (2004) Genetic ablation of caveolin-1 confers protection against atherosclerosis. Arterioscler Thromb Vasc Biol 24:98–105

    Article  PubMed  CAS  Google Scholar 

  • Frank PG, Hassan GS, Rodriguez-Feo JA, Lisanti MP (2007) Caveolae and caveolin-1: novel potential targets for the treatment of cardiovascular disease. Curr Pharm Des 13:1761–1769

    Article  PubMed  CAS  Google Scholar 

  • Gafencu A, Heltianu C, Burlacu A, Hunziker W, Simionescu M (2003) Investigation of IgG receptors expressed on the surface of human placental endothelial cells. Placenta 24:664–676

    Article  PubMed  CAS  Google Scholar 

  • Ge S, Song L, Serwanski DR, Kuziel WA, Pachter JS (2008) Transcellular transport of CCL2 across brain microvascular endothelial cells. J Neurochem 104:1219–1232

    Article  PubMed  CAS  Google Scholar 

  • Ghitescu L, Fixman A, Simionescu M, Simionescu N (1986) Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis. J Cell Biol 102:1304–1311

    Article  PubMed  CAS  Google Scholar 

  • Gradishar WJ (2006) Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother 7:1041–1053

    Article  PubMed  CAS  Google Scholar 

  • Hajjar DP, Haberland ME (1997) Lipoprotein trafficking in vascular cells—molecular Trojan horses and cellular saboteurs. J Biol Chem 272:22975–22978

    Article  PubMed  CAS  Google Scholar 

  • Hatakeyama T, Pappas PJ, Hobson RW 2nd, Boric MP, Sessa WC, Duran WN (2006) Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo. J Physiol (Lond) 574:275–281

    Article  CAS  Google Scholar 

  • Ikezu T, Ueda H, Trapp BD, Nishiyama K, Sha JF, Volonte D, Galbiati F, Byrd AL, Bassell G, Serizawa H, Lane WS, Lisanti MP, Okamoto T (1998) Affinity-purification and characterization of caveolins from the brain. Differential expression of caveolin-1, -2 and -3 in brain endothelial and astroglial cell types. Brain Res 804:177–192

    Article  PubMed  CAS  Google Scholar 

  • Jannin B, Menzel M, Berlot JP, Delmas D, Lancon A, Latruffe N (2004) Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake. Biochem Pharmacol 68:1113–1118

    Article  PubMed  CAS  Google Scholar 

  • Kim M-J, Dawes J, Jessup W (1994) Transendothelial transport of modified low-density lipoproteins. Atherosclerosis 108:5–17

    Article  PubMed  CAS  Google Scholar 

  • King GL, Johnson SM (1985) Receptor-mediated transport of insulin across endothelial cells. Science 227:1583–1586

    Article  PubMed  CAS  Google Scholar 

  • Krauss RM, Burke DJ (1982) Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res 23:97–104

    PubMed  CAS  Google Scholar 

  • Kumar P, Wu H, McBride JL, Jung KE, Kim MH, Davidson BL, Lee SK, Shankar P, Manjunath N (2007) Transvascular delivery of small interfering RNA to the central nervous system. Nature 448:39–43

    Article  PubMed  CAS  Google Scholar 

  • Lin MI, Yu J, Murata T, Sessa WC (2007) Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Res 67:2849–2856

    Article  PubMed  CAS  Google Scholar 

  • Lu W, Tan YZ, Hu KL, Jiang XG (2005) Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier. Int J Pharm 295:247–260

    Article  PubMed  CAS  Google Scholar 

  • Mehta D, Bhattacharya J, Matthay MA, Malik AB (2004) Integrated control of lung fluid balance. Am J Physiol Lung Cell Mol Physiol 287:L1081–L1090

    Article  PubMed  CAS  Google Scholar 

  • Minshall RD, Malik AB (2006) Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol 176:107–144

    Article  PubMed  Google Scholar 

  • Miyawaki-Shimizu K, Predescu D, Shimizu J, Broman M, Predescu S, Malik AB (2006) siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway. Am J Physiol Lung Cell Mol Physiol 290:L405–L413

    Article  PubMed  CAS  Google Scholar 

  • Murata T, Lin MI, Stan RV, Bauer PM, Yu J, Sessa WC (2007) Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells. J Biol Chem 282:16631–16643

    Article  PubMed  CAS  Google Scholar 

  • Nagase S, Shimamune K, Shumiya S (1979) Albumin-deficient rat mutant. Science 205:590–591

    Article  PubMed  CAS  Google Scholar 

  • Palade GE (1953) Fine structure of blood capillaries. J Appl Physics 24:1424

    Google Scholar 

  • Palade GE, Bruns RR (1968) Structural modification of plasmalemma vesicles. J Cell Biol 37:633–649

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (2007) shRNA and siRNA delivery to the brain. Adv Drug Deliv Rev 59:141–152

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM, Eisenberg J, Cefalu WT (1985) Absence of albumin receptor on brain capillaries in vivo or in vitro. Am J Physiol 249:E264–E267

    PubMed  CAS  Google Scholar 

  • Pascariu M, Bendayan M, Ghitescu L (2004) Correlated endothelial caveolin overexpression and increased transcytosis in experimental diabetes. J Histochem Cytochem 52:65–76

    PubMed  CAS  Google Scholar 

  • Predescu D, Vogel SM, Malik AB (2004) Functional and morphological studies of protein transcytosis in continuous endothelia. Am J Physiol Lung Cell Mol Physiol 287:L895–L901

    Article  PubMed  CAS  Google Scholar 

  • Quinlan GJ, Martin GS, Evans TW (2005) Albumin: biochemical properties and therapeutic potential. Hepatology 41:1211–1219

    Article  PubMed  CAS  Google Scholar 

  • Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H Jr, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138

    Article  PubMed  CAS  Google Scholar 

  • Rippe B, Rosengren BI, Carlsson O, Venturoli D (2002) Transendothelial transport: the vesicle controversy. J Vasc Res 39:375–390

    Article  PubMed  CAS  Google Scholar 

  • Schnitzer JE (1992) Gp60 is an albumin-binding glycoprotein expressed by continuous endothelium involved in albumin transcytosis. Am J Physiol 262:H246–H254

    PubMed  CAS  Google Scholar 

  • Schubert W, Frank PG, Razani B, Park DS, Chow CW, Lisanti MP (2001) Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. J Biol Chem 276:48619–48622

    Article  PubMed  CAS  Google Scholar 

  • Schubert W, Frank PG, Woodman SE, Hyogo H, Cohen DE, Chow CW, Lisanti MP (2002) Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 277:40091–40098

    Article  PubMed  CAS  Google Scholar 

  • Simionescu N, Simionescu M, Palade GE (1978) Open junctions in the endothelium of the postcapillary venules of the diaphragm. J Cell Biol 79:27–44

    Article  PubMed  CAS  Google Scholar 

  • Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J (2002) Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417:750–754

    Article  PubMed  CAS  Google Scholar 

  • Soda R, Tavassoli M (1984) Transendothelial transport (transcytosis) of iron-transferrin complex in the bone marrow. J Ultrastruct Res 88:18–29

    Article  PubMed  CAS  Google Scholar 

  • Song L, Ge S, Pachter JS (2007) Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells. Blood 109:1515–1523

    Article  PubMed  CAS  Google Scholar 

  • Stewart PA (2000) Endothelial vesicles in the blood-brain barrier: are they related to permeability? Cell Mol Neurobiol 20:149–163

    Article  PubMed  CAS  Google Scholar 

  • The Albumin Website (2008) http://www.albumin.org

  • Tiruppathi C, Song W, Bergenfeldt M, Sass P, Malik AB (1997) Gp60 activation mediates albumin transcytosis in endothelial cells by tyrosine kinase-dependent pathway. J Biol Chem 272:25968–25975

    Article  PubMed  CAS  Google Scholar 

  • Virgintino D, Robertson D, Errede M, Benagiano V, Tauer U, Roncali L, Bertossi M (2002) Expression of caveolin-1 in human brain microvessels. Neuroscience 115:145–152

    Article  PubMed  CAS  Google Scholar 

  • Watkins S, Madison J, Galliano M, Minchiotti L, Putnam FW (1994) Analbuminemia: three cases resulting from different point mutations in the albumin gene. Proc Natl Acad Sci USA 91:9417–9421

    Article  PubMed  CAS  Google Scholar 

  • Yamada E (1955) The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol 1:445–458

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Bergaya S, Murata T, Alp IF, Bauer MP, Lin MI, Drab M, Kurzchalia TV, Stan RV, Sessa WC (2006) Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J Clin Invest 116:1284–1291

    Article  PubMed  CAS  Google Scholar 

  • Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J, Chien KR (2002) Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci USA 99:11375–11380

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Philippe G. Frank or Michael P. Lisanti.

Additional information

P.G.F. is supported by grants from the W.W. Smith Charitable Trust Fund and the Susan G. Komen Foundation. M.P.L. is supported by grants from the National Institutes of Health and the American Heart Association.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frank, P.G., Pavlides, S. & Lisanti, M.P. Caveolae and transcytosis in endothelial cells: role in atherosclerosis. Cell Tissue Res 335, 41–47 (2009). https://doi.org/10.1007/s00441-008-0659-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-008-0659-8

Keywords

Navigation