The role of caveolae in endothelial cell dysfunction with a focus on nutrition and environmental toxicants.
Complications of vascular diseases, including atherosclerosis, are the number one cause of death in Western societies. Dysfunction of endothelial cells is a critical underlying cause of the pathology of atherosclerosis. Lipid rafts, and especially caveolae, are enriched in endothelial cells, and down-regulation of the caveolin-1 gene may provide protection against the development of atherosclerosis. There is substantial evidence that exposure to environmental pollution is linked to cardiovascular mortality, and that persistent organic pollutants can markedly contribute to endothelial cell dysfunction and an increase in vascular inflammation. Nutrition can modulate the toxicity of environmental pollutants, and evidence suggests that these affect health and disease outcome associated with chemical insults. Because caveolae can provide a regulatory platform for pro-inflammatory signalling associated with vascular diseases such as atherosclerosis, we suggest a link between atherogenic risk and functional changes of caveolae by environmental factors such as dietary lipids and organic pollutants. For example, we have evidence that endothelial caveolae play a role in uptake of persistent organic pollutants, an event associated with subsequent production of inflammatory mediators. Functional properties of caveolae can be modulated by nutrition, such as dietary lipids (e.g. fatty acids) and plant-derived polyphenols (e.g. flavonoids), which change activation of caveolae-associated signalling proteins. The following review will focus on caveolae providing a platform for pro-inflammatory signalling, and the role of caveolae in endothelial cell functional changes associated with environmental mediators such as nutrients and toxicants, which are known to modulate the pathology of vascular diseases.
Majkova
Zuzana
Z
Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA.
Toborek
Michal
M
Hennig
Bernhard
B
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D051379:Mice; D052756:Nutritional Sciences; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D015398:Signal Transduction
D051242:Caveolin 1; D004041:Dietary Fats; D004785:Environmental Pollutants; D005419:Flavonoids; D011084:Polycyclic Aromatic Hydrocarbons; D011078:Polychlorinated Biphenyls
Hypertension. 2008 Apr;51(4):1088-95
18259008
Clin Chem. 2008 Jan;54(1):24-38
18160725
Toxicol Sci. 1999 Dec;52(2):232-9
10630576
Biochem Biophys Res Commun. 1999 Feb 5;255(1):34-9
10082651
J Biol Chem. 2000 Jun 23;275(25):19416-21
10787410
QJM. 2003 Jul;96(7):465-80
12881589
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10339-43
7479780
Chem Biol Interact. 2008 Nov 25;176(2-3):71-8
18786521
Asia Pac J Clin Nutr. 2008;17 Suppl 1:131-4
18296320
Biochem Pharmacol. 2009 Feb 15;77(4):597-607
18983984
J Cardiovasc Pharmacol. 2009 Dec;54(6):468-76
19770673
Atherosclerosis. 2009 Nov;207(1):51-8
19409565
Ann Intern Med. 2001 Jun 19;134(12):1106-14
11412050
Toxicol Appl Pharmacol. 2002 Jun 15;181(3):174-83
12079426
Biochimie. 2007 Jan;89(1):169-77
17125900
Environ Int. 2010 Nov;36(8):931-4
19608276
J Biol Chem. 1997 Jul 25;272(30):18522-5
9228013
Am J Clin Nutr. 2004 May;79(5):727-47
15113710
Menopause. 2007 Sep-Oct;14(5):933-40
17667142
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5009-14
9560219
Toxicol Appl Pharmacol. 2009 Oct 15;240(2):299-305
19632255
Biochem Biophys Res Commun. 1997 Nov 7;240(1):1-7
9367871
Science. 2001 Sep 28;293(5539):2449-52
11498544
J Pharmacol Exp Ther. 2007 Oct;323(1):78-84
17636007
Am J Clin Nutr. 1994 Dec;60(6 Suppl):1017S-1022S
7977143
Cell Metab. 2009 Jul;10(1):48-54
19583953
Br J Nutr. 2008 Dec;100(6):1152-7
18492298
J Mol Cell Cardiol. 2008 May;44(5):938-47
18417152
J Biol Chem. 2000 Jul 21;275(29):22268-72
10781589
Am J Clin Nutr. 2007 Mar;85(3):895-909
17344514
Eur J Pharmacol. 2008 May 13;585(2-3):256-60
18423600
Science. 2002 Apr 19;296(5567):535-9
11964480
J Biol Chem. 1996 Mar 15;271(11):6518-22
8626455
J Cell Biol. 1995 Dec;131(6 Pt 1):1421-33
8522601
Nat Med. 2000 Dec;6(12):1362-7
11100121
J Neurochem. 2004 May;89(4):939-50
15140193
J Biol Chem. 2001 Dec 28;276(52):48619-22
11689550
J Cell Biol. 1995 May;129(3):619-27
7537273
Am J Physiol Cell Physiol. 2009 Mar;296(3):C403-13
19052258
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75
12588755
N Engl J Med. 1997 Apr 10;336(15):1066-71
9091804
Shock. 2004 Aug;22(2):120-30
15257084
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10517-21
1279683
J Lipid Res. 2006 Jul;47(7):1597-8
16645198
J Physiol Pharmacol. 2008 Dec;59 Suppl 9:217-35
19261982
Arch Biochem Biophys. 2007 Oct 15;466(2):250-9
17662956
J Biol Chem. 1997 Oct 10;272(41):25968-75
9325331
Arch Environ Contam Toxicol. 1999 Oct;37(3):408-14
10473799
Immunology. 2009 Jul;127(3):299-311
19538249
J Biol Chem. 2002 Feb 15;277(7):4925-31
11733519
Toxicol Appl Pharmacol. 2009 May 15;237(1):1-7
19265715
J Pharmacol Exp Ther. 2004 Jul;310(1):135-40
15054117
Metabolism. 2008 Oct;57(10):1328-39
18803934
Environ Health Perspect. 2008 Jun;116(6):761-8
18560532
Environ Health Perspect. 2005 Jan;113(1):83-7
15626652
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):98-105
14563650
Chem Phys Lipids. 2003 Nov;126(1):1-27
14580707
Cell Physiol Biochem. 2008;22(1-4):287-94
18769056
Mol Interv. 2003 Dec;3(8):445-64
14993453
Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1712-20
18385095
Am J Physiol Cell Physiol. 2005 Mar;288(3):C494-506
15692148
Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3340-7
17933968
Public Health Nutr. 2009 Jan;12(1):115-21
18410704
J Exp Med. 2007 Oct 1;204(10):2373-82
17893196
J Biol Chem. 1989 Dec 5;264(34):20163-6
2479645
Cancer Res. 2006 Nov 15;66(22):10805-14
17108117
Circulation. 2009 Sep 15;120(11):941-8
19720932
J Biol Chem. 1996 Nov 15;271(46):29182-90
8910575
J Biol Chem. 2001 Mar 16;276(11):8341-9
11112773
Am J Ind Med. 1997 Sep;32(3):234-9
9219652
Biochem J. 2000 Oct 1;351(Pt 1):257-64
10998369
Phytochemistry. 2008 Dec;69(18):3117-30
17869316
Toxicol Lett. 2009 Sep 10;189(2):96-101
19467301
Environ Health Perspect. 2007 Apr;115(4):493-5
17450213
Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):187-91
19502020
Cardiovasc Res. 2006 Apr 1;70(1):31-41
16540099
J Transl Med. 2009 Mar 25;7:22
19321006
Mol Pharmacol. 2007 Sep;72(3):553-62
17565002
Br J Nutr. 2008 Jan;99(1):12-22
17666146
Physiol Rev. 2004 Oct;84(4):1341-79
15383654
Cell. 2008 Jan 11;132(1):113-24
18191225
J Natl Cancer Inst. 2004 Nov 3;96(21):1577-84
15523086
Chem Phys Lipids. 2008 May;153(1):57-63
18343224
Biochem Biophys Res Commun. 2006 Feb 10;340(2):702-8
16380094
Lab Invest. 2009 Jun;89(6):695-707
19333233
J Cardiovasc Pharmacol. 2004 Aug;44(2):155-63
15243295
Cardiovasc Res. 2004 Nov 1;64(2):234-42
15485682
J Biol Chem. 2000 Apr 14;275(15):11278-83
10753938
Am J Prev Med. 2006 May;30(5):438-9; author reply 441-4
16627132
J Hypertens. 2006 Jan;24(1):75-84
16331104
J Immunol. 2006 Oct 1;177(7):4853-60
16982927
J Biol Chem. 2001 Apr 20;276(16):13442-51
11278309
J Biol Chem. 2007 Jun 1;282(22):16631-43
17416589
Invest Ophthalmol Vis Sci. 2007 Jan;48(1):18-26
17197511
Virchows Arch. 2007 Dec;451(6):1039-45
17851687
Annu Rev Pharmacol Toxicol. 2008;48:359-91
17914930
Cell Tissue Res. 2009 Jan;335(1):41-7
18688651
Pharmacol Rev. 2000 Dec;52(4):673-751
11121513
Biochemistry. 2004 Apr 13;43(14):4179-87
15065861
J Cell Biochem. 2009 Jun 1;107(3):460-72
19308997
J Biol Chem. 2001 Oct 12;276(41):38121-38
11457855
Mol Pharmacol. 2006 Oct;70(4):1174-83
16822931
Toxicol Sci. 2003 Nov;76(1):212-9
12970578
J Mol Endocrinol. 2007 Jun;38(6):603-18
17556531
Sheng Li Xue Bao. 2005 Jun 25;57(3):373-8
15968435
J Bone Miner Res. 2006 Oct;21(10):1637-47
16995819
Antioxid Redox Signal. 2009 Jul;11(7):1711-31
19257809
Environ Sci Technol. 2005 Nov 15;39(22):8622-9
16323755
Mol Cell Biol. 2002 Apr;22(7):2329-44
11884617
Chem Biol Interact. 2008 Mar 10;172(1):27-38
18155686
Biochemistry. 2003 Dec 30;42(51):15124-31
14690422
J Biol Chem. 2009 Nov 27;284(48):33255-64
19801678
Ann Ist Super Sanita. 2007;43(4):348-61
18209268
J Biol Chem. 1995 Jun 9;270(23):14214-9
7775482
Mol Biol Cell. 2002 Jul;13(7):2502-17
12134086
Clin Sci (Lond). 2007 Feb;112(3):183-91
17007611
Cell Calcium. 2009 Jun;45(6):625-33
19324409
Clin Physiol Biochem. 1984;2(2-3):123-34
6386279
J Lipid Res. 1998 May;39(5):1062-70
9610774
Br J Pharmacol. 1987 Nov;92(3):639-46
3322462
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2964-74
9409283
Annu Rev Nutr. 2004;24:511-38
15189130
Hum Mol Genet. 2000 Dec 12;9(20):3047-54
11115849
Am J Prev Med. 2005 Nov;29(4):335-46
16242600
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11375-80
12177436
Cell Signal. 2002 Feb;14(2):93-8
11781132
Am J Pathol. 2003 Jun;162(6):2059-68
12759260
J Nutr Biochem. 2009 Mar;20(3):202-9
18656337
J Cell Biol. 1994 Dec;127(5):1199-215
7962085
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5
1675786
Cell Tissue Res. 1998 Jul;293(1):101-10
9634602
Environ Health Perspect. 2007 Aug;115(8):1204-9
17687448
J Biophys Biochem Cytol. 1955 Sep 25;1(5):445-58
13263332
Toxicol Sci. 2003 Sep;75(1):47-56
12805654
Can J Physiol Pharmacol. 2008 Nov;86(11):761-9
19011671
FASEB J. 2007 May;21(7):1565-74
17272740
Mol Endocrinol. 2002 Jan;16(1):100-15
11773442
Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L114-24
16891390
Proc Soc Exp Biol Med. 1985 May;179(1):116-22
3921971
Cell. 1992 Feb 21;68(4):673-82
1739974
Mol Endocrinol. 2004 Nov;18(11):2660-71
15272054
Toxicol Appl Pharmacol. 2008 Oct 15;232(2):309-16
18671994
Environ Sci Technol. 2004 Oct 1;38(19):4945-9
15506184
FASEB J. 2004 Jun;18(9):1040-2
15084525
Carcinogenesis. 2008 Nov;29(11):2153-61
18635524
Cardiovasc Res. 2000 Oct;48(1):13-22
11033104
Aquat Toxicol. 2006 May 25;77(4):422-32
16500718
Trends Cell Biol. 1994 Jul;4(7):231-5
14731661
Nature. 1995 Sep 21;377(6546):239-42
7545787