Trends in Cardiovascular Medicine
Volume 15, Issue 5 , Pages 157-162 , July 2005

The Double Regulation of Endothelial Nitric Oxide Synthase by Caveolae and Caveolin: A Paradox Solved Through the Study of Angiogenesis

  • Elhem Sbaa
    • ,
  • Françoise Frérart
    • ,
  • Olivier Feron

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Olivier Feron, Unit of Pharmacology and Therapeutics (FATH 5349), UCL Medical School, B-1200 Brussels, Belgium. Tel.: (+32) 2-764-9326; fax: (+32) 2-764-9322

References 

  1. Ashburn JH, Baveja R, Kresge N, et al. Remote trauma sensitizes hepatic microcirculation to endothelin via caveolin inhibition of eNOS activity. Shock. 2004;22:120–130
  2. Attia DM, Feron O, Goldschmeding R, et al. Hypercholesterolemia in rats induces podocyte stress and decreases renal cortical nitric oxide synthesis via an angiotensin II type 1 receptor-sensitive mechanism. J Am Soc Nephrol. 2004;15:949–957
  3. Bauer PM, Yu J, Chen Y, et al. Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Proc Natl Acad Sci USA. 2005;102:204–209
  4. Blair A, Shaul PW, Yuhanna IS, et al. Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. J Biol Chem. 1999;274:32512–32519
  5. Brouet A, DeWever J, Martinive P, et al. Anti-tumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. FASEB J. 2005;19:602–604
  6. Brouet A, Sonveaux P, Dessy C, et al. Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res. 2001;89:866–873
  7. Bucci M, Gratton JP, Rudic RD, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med. 2000;6:1362–1367
  8. Bucci M, Roviezzo F, Brancaleone V, et al. Diabetic mouse angiopathy is linked to progressive sympathetic receptor deletion coupled to an enhanced caveolin-1 expression. Arterioscler Thromb Vasc Biol. 2004;24:721–726
  9. Couet J, Li S, Okamoto T, et al. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem. 1997;272:6525–6533
  10. Feron O, Belhassen L, Kobzik L, et al. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem. 1996;271:22810–22814
  11. Feron O, Dessy C, Desager JP, et al. Hydroxy-methylglutaryl-coenzyme A reductase inhibition promotes endothelial nitric oxide synthase activation through a decrease in caveolin abundance. Circulation. 2001;103:113–118
  12. Feron O, Dessy C, Moniotte S, et al. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest. 1999;103:897–905
  13. Feron O, Kelly RA. The caveolar paradox: suppressing, inducing, and terminating eNOS signaling. Circ Res. 2001;88:129–131
  14. Feron O, Saldana F, Michel JB, Michel T. The endothelial nitric-oxide synthase-caveolin regulatory cycle. J Biol Chem. 1998;273:3125–3128
  15. Garcia-Cardena G, Fan R, Stern DF, et al. Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1. J Biol Chem. 1996;271:27237–27240
  16. Garcia-Cardena G, Oh P, Liu J, et al. Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA. 1996;93:6448–6453
  17. Glenney JR. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989;264:20163–20166
  18. Gratton JP, Lin MI, Yu J, et al. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell. 2003;4:31–39
  19. Hare JM, Lofthouse RA, Juang GJ, et al. Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure. Circ Res. 2000;86:1085–1092
  20. Kobayashi N, Mori Y, Nakano S, et al. TCV-116 stimulates eNOS and caveolin-1 expression and improves coronary microvascular remodeling in normotensive and angiotensin II-induced hypertensive rats. Atherosclerosis. 2001;158:359–368
  21. Li H, Lewis A, Brodsky S, et al. Homocysteine induces 3-hydroxy-3-methylglutaryl coenzyme A reductase in vascular endothelial cells: a mechanism for development of atherosclerosis?. Circulation. 2002;105:1037–1043
  22. Li S, Couet J, Lisanti MP. Src tyrosine kinases, Gα subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem. 1996;271:29182–29190
  23. Lungu AO, Jin ZG, Yamawaki H, et al. Cyclosporin A inhibits flow-mediated activation of endothelial nitric-oxide synthase by altering cholesterol content in caveolae. J Biol Chem. 2004;279:48794–48800
  24. Martin S, Tesse A, Hugel B, et al. Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression. Circulation. 2004;109:1653–1659
  25. Michel T, Feron O. Nitric oxide synthases: which, where, how, and why?. J Clin Invest. 1997;100:2146–2152
  26. Michel JB, Feron O, Sacks D, Michel T. Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin. J Biol Chem. 1997;272:15583–15586
  27. Michel JB, Feron O, Sase K, et al. Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase. J Biol Chem. 1997;272:25907–25912
  28. Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in the modulation of angiogenesis. Curr Pharm Des. 2003;9:521–530
  29. Pelat M, Dessy C, Massion P, et al. Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprotein E−/− mice in vivo. Circulation. 2003;107:2480–2486
  30. Pelligrino DA, Ye S, Tan F, et al. Nitric-oxide-dependent pial arteriolar dilation in the female rat: effects of chronic estrogen depletion and repletion. Biochem Biophys Res Commun. 2000;269:165–171
  31. Piech A, Dessy C, Havaux X, et al. Differential regulation of nitric oxide synthases and their allosteric regulators in heart and vessels of hypertensive rats. Cardiovasc Res. 2003;57:456–467
  32. Piech A, Massart PE, Dessy C, et al. Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy. Am J Physiol. 2002;282:H219–H231
  33. Ratajczak P, Damy T, Heymes C, et al. Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat. Cardiovasc Res. 2003;57:358–369
  34. Razani B, Woodman SE, Lisanti MP. Caveolae: from cell biology to animal physiology. Pharmacol Rev. 2002;54:431–467
  35. Rizzo V, Morton C, DePaola N, et al. Recruitment of endothelial caveolae into mechanotransduction pathways by flow conditioning in vitro. Am J Physiol Heart Circ Physiol. 2003;285:H1720–H1729
  36. Rothberg KG, Heuser JE, Donzell WC, et al. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68:673–682
  37. Shah V, Cao S, Hendrickson H, et al. Regulation of hepatic eNOS by caveolin and calmodulin after bile duct ligation in rats. Am J Physiol. 2001;280:G1209–G1216
  38. Shaul PW, Smart EJ, Robinson LJ, et al. Acylation targets endothelial nitric-oxide synthase to plasmalemmal caveolae. J Biol Chem. 1996;271:6518–6522
  39. Shi Y, Pritchard KA, Holman P, et al. Chronic myocardial hypoxia increases nitric oxide synthase and decreases caveolin-3. Free Radic Biol Med. 2000;29:695–703
  40. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1:31–39
  41. Sobey CG, Weiler JM, Boujaoude M, Woodman OL. Effect of short-term phytoestrogen treatment in male rats on nitric oxide-mediated responses of carotid and cerebral arteries: comparison with 17beta-estradiol. J Pharmacol Exp Ther. 2004;310:135–140
  42. Sonveaux P, Martinive P, DeWever J, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ Res. 2004;95:154–161
  43. Thompson MA, Henderson KK, Woodman CR, et al. Exercise preserves endothelium-dependent relaxation in coronary arteries of hypercholesterolemic male pigs. J Appl Physiol. 2004;96:1114–1126
  44. Uittenbogaard A, Shaul PW, Yuhanna IS, et al. High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J Biol Chem. 2000;275:11278–11283
  45. Uray IP, Connelly JH, Frazier OH, et al. Mechanical unloading increases caveolin expression in the failing human heart. Cardiovasc Res. 2003;59:57–66
  46. Wang X, Abdel-Rahman AA. Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts. Am J Physiol. 2002;282:H2309–H2315
  47. Yamada EE. The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol. 1955;1:445–458
  48. Yokomori H, Oda M, Ogi M, et al. Enhanced expression of endothelial nitric oxide synthase and caveolin-1 in human cirrhosis. Liver. 2002;22:150–158
  49. Zhu Y, Liao HL, Niu XL, et al. Low density lipoprotein induces eNOS translocation to membrane caveolae: the role of RhoA activation and stress fiber formation. Biochim Biophys Acta. 2003;1635:117–126

PII: S1050-1738(05)00060-5

doi: 10.1016/j.tcm.2005.05.006

Trends in Cardiovascular Medicine
Volume 15, Issue 5 , Pages 157-162 , July 2005

Article Tools

* Image Usage & Resolution