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Caveolin-1/-3: therapeutic targets for myocardial ischemia/reperfusion injury

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Abstract

Myocardial ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality worldwide. Caveolae, caveolin-1 (Cav-1), and caveolin-3 (Cav-3) are essential for the protective effects of conditioning against myocardial I/R injury. Caveolins are membrane-bound scaffolding proteins that compartmentalize and modulate signal transduction. In this review, we introduce caveolae and caveolins and briefly describe the interactions of caveolins in the cardiovascular diseases. We also review the roles of Cav-1/-3 in protection against myocardial ischemia and I/R injury, and in conditioning. Finally, we suggest several potential research avenues that may be of interest to clinicians and basic scientists. The information included, herein, is potentially useful for the design of future studies and should advance the investigation of caveolins as therapeutic targets.

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Abbreviations

Akt:

Protein kinase B

APC:

Anesthetic preconditioning

Cav:

Caveolin

CSD:

Caveolin scaffolding domain

eNOS:

Endothelial nitric oxide synthase

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

GPCRs:

G protein-coupled receptors

GSK3β:

Glycogen synthase kinase-3β

HO-1:

Heme oxygenase-1

IPC:

Ischemic preconditioning

IPTC:

Ischemic postconditioning

I/R:

Ischemia/reperfusion

KO:

Knockout

MAPKs:

Mitogen-activated protein kinases

mPTP:

Mitochondrial permeability transition pore

OE:

Overexpression

PI3K:

Phosphoinositide-3 kinase

PKC:

Protein kinase C

RISK:

Reperfusion injury salvage kinase

SAFE:

Survivor activating factor enhancement

References

  1. Ahn M, Kim H, Matsumoto Y, Shin T (2006) Increased expression of caveolin-1 and -2 in the hearts of Lewis rats with experimental autoimmune myocarditis. Autoimmunity 39:489–495. doi:10.1080/08916930600929321

    Article  CAS  PubMed  Google Scholar 

  2. Alcalay Y, Hochhauser E, Kliminski V, Dick J, Zahalka MA, Parnes D, Schlesinger H, Abassi Z, Shainberg A, Schindler RF, Brand T, Kessler-Icekson G (2013) Popeye domain containing 1 (Popdc1/Bves) is a caveolae-associated protein involved in ischemia tolerance. PLoS One 8:e71100. doi:10.1371/journal.pone.0071100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Anderson RG, Jacobson K (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296:1821–1825. doi:10.1126/science.1068886

    Article  CAS  PubMed  Google Scholar 

  4. Ballard-Croft C, Locklar AC, Kristo G, Lasley RD (2006) Regional myocardial ischemia-induced activation of MAPKs is associated with subcellular redistribution of caveolin and cholesterol. Am J Physiol Heart Circ Physiol 291:H658–H667. doi:10.1152/ajpheart.01354.2005

    Article  CAS  PubMed  Google Scholar 

  5. Bernatchez P, Sharma A, Bauer PM, Marin E, Sessa WC (2011) A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice. J Clin Invest 121:3747–3755. doi:10.1172/JCI44778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bielawska AE, Shapiro JP, Jiang L, Melkonyan HS, Piot C, Wolfe CL, Tomei LD, Hannun YA, Umansky SR (1997) Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion. Am J Pathol 151:1257–1263

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM (2005) Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 54:146–151

    Article  CAS  PubMed  Google Scholar 

  8. Bulluck H, Hausenloy DJ (2015) Ischaemic conditioning: are we there yet? Heart 101:1067–1077. doi:10.1136/heartjnl-2014-306531

    Article  PubMed  Google Scholar 

  9. Cao CM, Zhang Y, Weisleder N, Ferrante C, Wang X, Lv F, Zhang Y, Song R, Hwang M, Jin L, Guo J, Peng W, Li G, Nishi M, Takeshima H, Ma J, Xiao RP (2010) MG53 constitutes a primary determinant of cardiac ischemic preconditioning. Circulation 121:2565–2574. doi:10.1161/circulationaha.110.954628

    Article  CAS  PubMed  Google Scholar 

  10. Cao T, Gao Z, Gu L, Chen M, Yang B, Cao K, Huang H, Li M (2014) AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts. PLoS One 9:e103793. doi:10.1371/journal.pone.0103793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Cason BA, Gamperl AK, Slocum RE, Hickey RF (1997) Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology 87:1182–1190. doi:10.1097/00000542-199711000-00023

    Article  CAS  PubMed  Google Scholar 

  12. Chaudhary KR, Cho WJ, Yang F, Samokhvalov V, El-Sikhry HE, Daniel EE, Seubert JM (2013) Effect of ischemia reperfusion injury and epoxyeicosatrienoic acids on caveolin expression in mouse myocardium. J Cardiovasc Pharmacol 61:258–263. doi:10.1097/FJC.0b013e31827afcee

    Article  CAS  PubMed  Google Scholar 

  13. Chung TH, Wang SM, Liang JY, Yang SH, Wu JC (2009) The interaction of estrogen receptor alpha and caveolin-3 regulates connexin43 phosphorylation in metabolic inhibition-treated rat cardiomyocytes. Int J Biochem Cell Biol 41:2323–2333. doi:10.1016/j.biocel.2009.06.001

    Article  CAS  PubMed  Google Scholar 

  14. Das M, Cui J, Das DK (2007) Generation of survival signal by differential interaction of p38MAPKalpha and p38MAPKbeta with caveolin-1 and caveolin-3 in the adapted heart. J Mol Cell Cardiol 42:206–213. doi:10.1016/j.yjmcc.2006.08.118

    Article  CAS  PubMed  Google Scholar 

  15. Das M, Das S, Lekli I, Das DK (2012) Caveolin induces cardioprotection through epigenetic regulation. J Cell Mol Med 16:888–895. doi:10.1111/j.1582-4934.2011.01372.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Das M, Das S, Wang P, Powell SR, Das DK (2008) Caveolin and proteasome in tocotrienol mediated myocardial protection. Cell Physiol Biochem 22:287–294. doi:10.1159/000149807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Das M, Gherghiceanu M, Lekli I, Mukherjee S, Popescu LM, Das DK (2008) Essential role of lipid raft in ischemic preconditioning. Cell Physiol Biochem 21:325–334. doi:10.1159/000129391

    Article  CAS  PubMed  Google Scholar 

  18. de Marco MC, Kremer L, Albar JP, Martinez-Menarguez JA, Ballesta J, Garcia-Lopez MA, Marazuela M, Puertollano R, Alonso MA (2001) BENE, a novel raft-associated protein of the MAL proteolipid family, interacts with caveolin-1 in human endothelial-like ECV304 cells. J Biol Chem 276:23009–23017. doi:10.1074/jbc.M009739200

    Article  PubMed  Google Scholar 

  19. Der P, Cui J, Das DK (2006) Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts. J Mol Cell Cardiol 40:313–320. doi:10.1016/j.yjmcc.2005.10.005

    Article  CAS  PubMed  Google Scholar 

  20. 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. doi:10.1126/science.1062688

    Article  CAS  PubMed  Google Scholar 

  21. Feron O, Balligand JL (2006) Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res 69:788–797. doi:10.1016/j.cardiores.2005.12.014

    Article  CAS  PubMed  Google Scholar 

  22. Fiedler K, Parton RG, Kellner R, Etzold T, Simons K (1994) VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in epithelial cells. EMBO J 13:1729–1740

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Fridolfsson HN, Kawaraguchi Y, Ali SS, Panneerselvam M, Niesman IR, Finley JC, Kellerhals SE, Migita MY, Okada H, Moreno AL, Jennings M, Kidd MW, Bonds JA, Balijepalli RC, Ross RS, Patel PM, Miyanohara A, Chen Q, Lesnefsky EJ, Head BP, Roth DM, Insel PA, Patel HH (2012) Mitochondria-localized caveolin in adaptation to cellular stress and injury. FASEB J 26:4637–4649. doi:10.1096/fj.12-215798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gandolfini MP, Coupaye M, Bouaziz E, Dehoux M, Hajage D, Lacorte JM, Ledoux S (2015) Cardiovascular changes after gastric bypass surgery: involvement of increased secretions of glucagon-like peptide-1 and brain natriuretic peptide. Obes Surg. doi:10.1007/s11695-015-1643-5

    PubMed  Google Scholar 

  25. Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, Lisanti MP, Sessa WC (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem 272:25437–25440. doi:10.1074/jbc.272.41.25437

    Article  CAS  PubMed  Google Scholar 

  26. Gazzerro E, Sotgia F, Bruno C, Lisanti MP, Minetti C (2010) Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet 18:137–145. doi:10.1038/ejhg.2009.103

    Article  CAS  PubMed  Google Scholar 

  27. Giusti B, Marini M, Rossi L, Lapini I, Magi A, Capalbo A, Lapalombella R, di Tullio S, Samaja M, Esposito F, Margonato V, Boddi M, Abbate R, Veicsteinas A (2009) Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection. BMC Genom 10:342. doi:10.1186/1471-2164-10-342

    Article  CAS  Google Scholar 

  28. Glenney JR Jr, Zokas L (1989) Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton. J Cell Biol 108:2401–2408. doi:10.1083/jcb.108.6.2401

    Article  CAS  PubMed  Google Scholar 

  29. Hagiwara Y, Sasaoka T, Araishi K, Imamura M, Yorifuji H, Nonaka I, Ozawa E, Kikuchi T (2000) Caveolin-3 deficiency causes muscle degeneration in mice. Hum Mol Genet 9:3047–3054. doi:10.1093/hmg/9.20.3047

    Article  CAS  PubMed  Google Scholar 

  30. Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46:821–831. doi:10.1016/j.yjmcc.2009.02.021

    Article  CAS  PubMed  Google Scholar 

  31. Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75. doi:10.1016/j.tcm.2005.03.001

    Article  CAS  PubMed  Google Scholar 

  32. Hausenloy DJ, Yellon DM (2011) The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol 8:619–629. doi:10.1038/nrcardio.2011.85

    Article  CAS  PubMed  Google Scholar 

  33. Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, Hori H, Koga Y, Oka N, Imaizumi T, Yasunami M, Kimura A (2004) Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun 313:178–184. doi:10.1016/j.bbrc.2003.11.101

    Article  CAS  PubMed  Google Scholar 

  34. Head BP, Patel HH, Roth DM, Lai NC, Niesman IR, Farquhar MG, Insel PA (2005) G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J Biol Chem 280:31036–31044. doi:10.1074/jbc.M502540200

    Article  CAS  PubMed  Google Scholar 

  35. Hernandez-Resendiz S, Zazueta C (2014) PHO-ERK1/2 interaction with mitochondria regulates the permeability transition pore in cardioprotective signaling. Life Sci 108:13–21. doi:10.1016/j.lfs.2014.04.037

    Article  CAS  PubMed  Google Scholar 

  36. Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. doi:10.1161/circresaha.116.305348

    Article  CAS  PubMed  Google Scholar 

  37. Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D (2015) Remote ischemic conditioning. J Am Coll Cardiol 65:177–195. doi:10.1016/j.jacc.2014.10.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hnasko R, Lisanti MP (2003) The biology of caveolae: lessons from caveolin knockout mice and implications for human disease. Mol Interv 3:445–464. doi:10.1124/mi.3.8.445

    Article  CAS  PubMed  Google Scholar 

  39. Horikawa YT, Panneerselvam M, Kawaraguchi Y, Tsutsumi YM, Ali SS, Balijepalli RC, Murray F, Head BP, Niesman IR, Rieg T, Vallon V, Insel PA, Patel HH, Roth DM (2011) Cardiac-specific overexpression of caveolin-3 attenuates cardiac hypertrophy and increases natriuretic peptide expression and signaling. J Am Coll Cardiol 57:2273–2283. doi:10.1016/j.jacc.2010.12.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Horikawa YT, Patel HH, Tsutsumi YM, Jennings MM, Kidd MW, Hagiwara Y, Ishikawa Y, Insel PA, Roth DM (2008) Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury. J Mol Cell Cardiol 44:123–130. doi:10.1016/j.yjmcc.2007.10.003

    Article  CAS  PubMed  Google Scholar 

  41. Hsieh SR, Hsu CS, Lu CH, Chen WC, Chiu CH, Liou YM (2013) Epigallocatechin-3-gallate-mediated cardioprotection by Akt/GSK-3beta/caveolin signalling in H9c2 rat cardiomyoblasts. J Biomed Sci 20:86. doi:10.1186/1423-0127-20-86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hsieh SR, Tsai DC, Chen JY, Tsai SW, Liou YM (2009) Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation. Pflugers Arch 458:631–642. doi:10.1007/s00424-009-0655-1

    Article  CAS  PubMed  Google Scholar 

  43. Jasmin JF, Rengo G, Lymperopoulos A, Gupta R, Eaton GJ, Quann K, Gonzales DM, Mercier I, Koch WJ, Lisanti MP (2011) Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction. Am J Physiol Heart Circ Physiol 300:H1274–H1281. doi:10.1152/ajpheart.01173.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792. doi:10.1172/jci29126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC (1997) Isoflurane mimics ischemic preconditioning via activation of K(ATP) channels: reduction of myocardial infarct size with an acute memory phase. Anesthesiology 87:361–370. doi:10.1097/00000542-199708000-00024

    Article  CAS  PubMed  Google Scholar 

  46. Kim HA, Kim KH, Lee RA (2006) Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. Exp Mol Pathol 80:165–170. doi:10.1016/j.yexmp.2005.09.001

    Article  CAS  PubMed  Google Scholar 

  47. Koneru S, Penumathsa SV, Thirunavukkarasu M, Samuel SM, Zhan L, Han Z, Maulik G, Das DK, Maulik N (2007) Redox regulation of ischemic preconditioning is mediated by the differential activation of caveolins and their association with eNOS and GLUT-4. Am J Physiol Heart Circ Physiol 292:H2060–H2072. doi:10.1152/ajpheart.01169.2006

    Article  CAS  PubMed  Google Scholar 

  48. Krajewska WM, Maslowska I (2004) Caveolins: structure and function in signal transduction. Cell Mol Biol Lett 9:195–220

    CAS  PubMed  Google Scholar 

  49. Lacerda L, Somers S, Opie LH, Lecour S (2009) Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway. Cardiovasc Res 84:201–208. doi:10.1093/cvr/cvp274

    Article  CAS  PubMed  Google Scholar 

  50. Lamont KT, Somers S, Lacerda L, Opie LH, Lecour S (2011) Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection. J Pineal Res 50:374–380. doi:10.1111/j.1600-079X.2010.00853.x

    Article  CAS  PubMed  Google Scholar 

  51. Lang XE, Wang X, Zhang KR, Lv JY, Jin JH, Li QS (2013) Isoflurane preconditioning confers cardioprotection by activation of ALDH2. PLoS One 8:e52469. doi:10.1371/journal.pone.0052469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li S, Okamoto T, Chun M, Sargiacomo M, Casanova JE, Hansen SH, Nishimoto I, Lisanti MP (1995) Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J Biol Chem 270:15693–15701

    Article  CAS  PubMed  Google Scholar 

  53. Liou YM, Hsieh SR, Wu TJ, Chen JY (2010) Green tea extract given before regional myocardial ischemia–reperfusion in rats improves myocardial contractility by attenuating calcium overload. Pflugers Arch 460:1003–1014. doi:10.1007/s00424-010-0881-6

    Article  CAS  PubMed  Google Scholar 

  54. Lisanti MP, Scherer PE, Vidugiriene J, Tang Z, Hermanowski-Vosatka A, Tu YH, Cook RF, Sargiacomo M (1994) Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol 126:111–126. doi:10.1083/jcb.126.1.111

    Article  CAS  PubMed  Google Scholar 

  55. Lochner A, Huisamen B, Nduhirabandi F (2013) Cardioprotective effect of melatonin against ischaemia/reperfusion damage. Front Biosci (Elite Ed) 5:305–315

    Article  Google Scholar 

  56. Lu Q, Yi X, Cheng X, Sun X, Yang X (2014) Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide. In Vitro Cell Dev Biol Anim 51:353–360. doi:10.1007/s11626-014-9844-0

    Article  PubMed  CAS  Google Scholar 

  57. Mayor S, Rao M (2004) Rafts: scale-dependent, active lipid organization at the cell surface. Traffic 5:231–240. doi:10.1111/j.1600-0854.2004.00172.x

    Article  CAS  PubMed  Google Scholar 

  58. Minetti C, Bado M, Broda P, Sotgia F, Bruno C, Galbiati F, Volonte D, Lucania G, Pavan A, Bonilla E, Lisanti MP, Cordone G (2002) Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency. Am J Pathol 160:265–270. doi:10.1016/s0002-9440(10)64370-2

    Article  PubMed  PubMed Central  Google Scholar 

  59. Mora R, Bonilha VL, Marmorstein A, Scherer PE, Brown D, Lisanti MP, Rodriguez-Boulan E (1999) Caveolin-2 localizes to the golgi complex but redistributes to plasma membrane, caveolae, and rafts when co-expressed with caveolin-1. J Biol Chem 274:25708–25717. doi:10.1074/jbc.274.36.25708

    Article  CAS  PubMed  Google Scholar 

  60. Ohsawa Y, Toko H, Katsura M, Morimoto K, Yamada H, Ichikawa Y, Murakami T, Ohkuma S, Komuro I, Sunada Y (2004) Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility in association with increased endothelial nitric oxide synthase activity. Hum Mol Genet 13:151–157. doi:10.1093/hmg/ddh014

    Article  CAS  PubMed  Google Scholar 

  61. Oka N, Yamamoto M, Schwencke C, Kawabe J, Ebina T, Ohno S, Couet J, Lisanti MP, Ishikawa Y (1997) Caveolin interaction with protein kinase C. Isoenzyme-dependent regulation of kinase activity by the caveolin scaffolding domain peptide. J Biol Chem 272:33416–33421. doi:10.1074/jbc.272.52.33416

    Article  CAS  PubMed  Google Scholar 

  62. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M, Ogata H, Tokuyama K, Ueki K, Nagano T, Tanaka A, Yokoyama S, Kadowaki T (2013) A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503:493–499. doi:10.1038/nature12656

    Article  CAS  PubMed  Google Scholar 

  63. Ovize M, Baxter GF, Di Lisa F, Ferdinandy P, Garcia-Dorado D, Hausenloy DJ, Heusch G, Vinten-Johansen J, Yellon DM, Schulz R (2010) Postconditioning and protection from reperfusion injury: where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 87:406–423. doi:10.1093/cvr/cvq129

    Article  CAS  PubMed  Google Scholar 

  64. Panneerselvam M, Patel HH, Roth DM (2012) Caveolins and heart diseases. Adv Exp Med Biol 729:145–156. doi:10.1007/978-1-4614-1222-9_10

    Article  CAS  PubMed  Google Scholar 

  65. Park DS, Woodman SE, Schubert W, Cohen AW, Frank PG, Chandra M, Shirani J, Razani B, Tang B, Jelicks LA, Factor SM, Weiss LM, Tanowitz HB, Lisanti MP (2002) Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol 160:2207–2217. doi:10.1016/s0002-9440(10)61168-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Parolini I, Sargiacomo M, Galbiati F, Rizzo G, Grignani F, Engelman JA, Okamoto T, Ikezu T, Scherer PE, Mora R, Rodriguez-Boulan E, Peschle C, Lisanti MP (1999) Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the Golgi complex. J Biol Chem 274:25718–25725. doi:10.1074/jbc.274.36.25718

    Article  CAS  PubMed  Google Scholar 

  67. Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8:185–194. doi:10.1038/nrm2122

    Article  CAS  PubMed  Google Scholar 

  68. Patel HH, Head BP, Petersen HN, Niesman IR, Huang D, Gross GJ, Insel PA, Roth DM (2006) Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors. Am J Physiol Heart Circ Physiol 291:H344–H350. doi:10.1152/ajpheart.01100.2005

    Article  CAS  PubMed  Google Scholar 

  69. Patel HH, Murray F, Insel PA (2008) Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annu Rev Pharmacol Toxicol 48:359–391. doi:10.1146/annurev.pharmtox.48.121506.124841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Patel HH, Tsutsumi YM, Head BP, Niesman IR, Jennings M, Horikawa Y, Huang D, Moreno AL, Patel PM, Insel PA, Roth DM (2007) Mechanisms of cardiac protection from ischemia/reperfusion injury: a role for caveolae and caveolin-1. FASEB J 21:1565–1574. doi:10.1096/fj.06-7719com

    Article  CAS  PubMed  Google Scholar 

  71. Pawson T, Scott JD (1997) Signaling through scaffold, anchoring, and adaptor proteins. Science 278:2075–2080. doi:10.1126/science.278.5346.2075

    Article  CAS  PubMed  Google Scholar 

  72. Peart JN, Gross ER, Gross GJ (2005) Opioid-induced preconditioning: recent advances and future perspectives. Vascul Pharmacol 42:211–218. doi:10.1016/j.vph.2005.02.003

    Article  CAS  PubMed  Google Scholar 

  73. Peart JN, Pepe S, Reichelt ME, Beckett N, See Hoe L, Ozberk V, Niesman IR, Patel HH, Headrick JP (2014) Dysfunctional survival-signaling and stress-intolerance in aged murine and human myocardium. Exp Gerontol 50:72–81. doi:10.1016/j.exger.2013.11.015

    Article  PubMed  Google Scholar 

  74. Raikar LS, Vallejo J, Lloyd PG, Hardin CD (2006) Overexpression of caveolin-1 results in increased plasma membrane targeting of glycolytic enzymes: the structural basis for a membrane associated metabolic compartment. J Cell Biochem 98:861–871. doi:10.1002/jcb.20732

    Article  CAS  PubMed  Google Scholar 

  75. Rassaf T, Schulz R (2015) Mitochondrias’ sense of SNO-pathway to cardioprotection in ischemic preconditioning. Cardiovasc Res 106:182–183. doi:10.1093/cvr/cvv115

    Article  PubMed  Google Scholar 

  76. Ratajczak P, Damy T, Heymes C, Oliviero P, Marotte F, Robidel E, Sercombe R, Boczkowski J, Rappaport L, Samuel JL (2003) Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat. Cardiovasc Res 57:358–369. doi:10.1016/S0008-6363(02)00660-0

    Article  CAS  PubMed  Google Scholar 

  77. Razani B, Wang XB, Engelman JA, Battista M, Lagaud G, Zhang XL, Kneitz B, Hou H Jr, Christ GJ, Edelmann W, Lisanti MP (2002) Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Mol Cell Biol 22:2329–2344. doi:10.1128/MCB.22.7.2329-2344.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–467. doi:10.1124/pr.54.3.431

    Article  CAS  PubMed  Google Scholar 

  79. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682. doi:10.1016/0092-8674(92)90143-Z

    Article  CAS  PubMed  Google Scholar 

  80. Ruiz-Meana M, Nunez E, Miro-Casas E, Martinez-Acedo P, Barba I, Rodriguez-Sinovas A, Inserte J, Fernandez-Sanz C, Hernando V, Vazquez J, Garcia-Dorado D (2014) Ischemic preconditioning protects cardiomyocyte mitochondria through mechanisms independent of cytosol. J Mol Cell Cardiol 68:79–88. doi:10.1016/j.yjmcc.2014.01.001

    Article  CAS  PubMed  Google Scholar 

  81. Salzer U, Prohaska R (2001) Stomatin, flotillin-1, and flotillin-2 are major integral proteins of erythrocyte lipid rafts. Blood 97:1141–1143. doi:10.1182/blood.V97.4.1141

    Article  CAS  PubMed  Google Scholar 

  82. Sanguinetti AR, Cao H, Corley Mastick C (2003) Fyn is required for oxidative- and hyperosmotic-stress-induced tyrosine phosphorylation of caveolin-1. Biochem J 376:159–168. doi:10.1042/bj20030336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Sanguinetti AR, Mastick CC (2003) c-Abl is required for oxidative stress-induced phosphorylation of caveolin-1 on tyrosine 14. Cell Signal 15:289–298. doi:10.1016/S0898-6568(02)00090-6

    Article  CAS  PubMed  Google Scholar 

  84. Sanon VP, Sawaki D, Mjaatvedt CH, Jourdan-Le Saux C (2015) Myocardial tissue caveolae. Compr Physiol 5:871–886. doi:10.1002/cphy.c140050

    Article  PubMed  Google Scholar 

  85. Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP (1996) Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA 93:131–135. doi:10.1073/pnas.93.1.131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Schilling JM, Horikawa YT, Zemljic-Harpf AE, Vincent KP, Tyan L, Yu JK, McCulloch AD, Balijepalli RC, Patel HH, Roth DM (2016) Electrophysiology and metabolism of caveolin-3-overexpressing mice. Basic Res Cardiol 111:28. doi:10.1007/s00395-016-0542-9

    Article  PubMed  CAS  Google Scholar 

  87. Schilling JM, Roth DM, Patel HH (2015) Caveolins in cardioprotection—translatability and mechanisms. Br J Pharmacol 172:2114–2125. doi:10.1111/bph.13009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schultz JE, Hsu AK, Gross GJ (1998) Ischemic preconditioning in the intact rat heart is mediated by delta 1- but not mu- or kappa-opioid receptors. Circulation 97:1282–1289. doi:10.1161/01.CIR.97.13.1282

    Article  CAS  PubMed  Google Scholar 

  89. See Hoe LE, Schilling JM, Tarbit E, Kiessling CJ, Busija AR, Niesman IR, Du Toit E, Ashton KJ, Roth DM, Headrick JP, Patel HH, Peart JN (2014) Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection. Am J Physiol Heart Circ Physiol 307:H895–H903. doi:10.1152/ajpheart.00081.2014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Sehirli AO, Koyun D, Tetik S, Ozsavci D, Yiginer O, Cetinel S, Tok OE, Kaya Z, Akkiprik M, Kilic E, Sener G (2013) Melatonin protects against ischemic heart failure in rats. J Pineal Res 55:138–148. doi:10.1111/jpi.12054

    Article  CAS  PubMed  Google Scholar 

  91. Shahabi P, Siest G, Visvikis-siest S (2014) Influence of inflammation on cardiovascular protective effects of cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids. Drug Metab Rev 46:33–56. doi:10.3109/03602532.2013.837916

    Article  CAS  PubMed  Google Scholar 

  92. Shi Y, Pritchard KA Jr, Holman P, Rafiee P, Griffith OW, Kalyanaraman B, Baker JE (2000) Chronic myocardial hypoxia increases nitric oxide synthase and decreases caveolin-3. Free Radic Biol Med 29:695–703. doi:10.1016/S0891-5849(00)00364-6

    Article  CAS  PubMed  Google Scholar 

  93. Shimizu T, Suzuki S, Sato A, Nakamura Y, Ikeda K, Saitoh SI, Misaka S, Shishido T, Kubota I, Takeishi Y (2015) Cardio-protective effects of pentraxin 3 produced from bone marrow-derived cells against ischemia/reperfusion injury. J Mol Cell Cardiol 89:306–313. doi:10.1016/j.yjmcc.2015.10.013

    Article  CAS  PubMed  Google Scholar 

  94. Shiomi M, Miyamae M, Takemura G, Kaneda K, Inamura Y, Onishi A, Koshinuma S, Momota Y, Minami T, Figueredo VM (2014) Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult. Eur J Pharmacol 724:58–66. doi:10.1016/j.ejphar.2013.12.027

    Article  CAS  PubMed  Google Scholar 

  95. Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP (1999) Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 19:7289–7304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Sonne DP, Engstrom T, Treiman M (2008) Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia–reperfusion injury in rat heart. Regul Pept 146:243–249. doi:10.1016/j.regpep.2007.10.001

    Article  CAS  PubMed  Google Scholar 

  97. Sotgia F, Martinez-Outschoorn UE, Howell A, Pestell RG, Pavlides S, Lisanti MP (2012) Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms. Annu Rev Pathol 7:423–467. doi:10.1146/annurev-pathol-011811-120856

    Article  CAS  PubMed  Google Scholar 

  98. Sun J, Nguyen T, Aponte AM, Menazza S, Kohr MJ, Roth DM, Patel HH, Murphy E, Steenbergen C (2015) Ischaemic preconditioning preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria. Cardiovasc Res 106:227–236. doi:10.1093/cvr/cvv044

    Article  PubMed  PubMed Central  Google Scholar 

  99. Swaney JS, Patel HH, Yokoyama U, Head BP, Roth DM, Insel PA (2006) Focal adhesions in (myo)fibroblasts scaffold adenylyl cyclase with phosphorylated caveolin. J Biol Chem 281:17173–17179. doi:10.1074/jbc.M513097200

    Article  CAS  PubMed  Google Scholar 

  100. Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP (1996) Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J Biol Chem 271:2255–2261

    Article  CAS  PubMed  Google Scholar 

  101. Tonkovic-Capin M, Gross GJ, Bosnjak ZJ, Tweddell JS, Fitzpatrick CM, Baker JE (2002) Delayed cardioprotection by isoflurane: role of K(ATP) channels. Am J Physiol Heart Circ Physiol 283:H61–H68. doi:10.1152/ajpheart.01040.2001

    Article  CAS  PubMed  Google Scholar 

  102. Tsutsumi YM, Horikawa YT, Jennings MM, Kidd MW, Niesman IR, Yokoyama U, Head BP, Hagiwara Y, Ishikawa Y, Miyanohara A, Patel PM, Insel PA, Patel HH, Roth DM (2008) Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning. Circulation 118:1979–1988. doi:10.1161/circulationaha.108.788331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Tsutsumi YM, Kawaraguchi Y, Horikawa YT, Niesman IR, Kidd MW, Chin-Lee B, Head BP, Patel PM, Roth DM, Patel HH (2010) Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection. Anesthesiology 112:1136–1145. doi:10.1097/ALN.0b013e3181d3d624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Tsutsumi YM, Kawaraguchi Y, Niesman IR, Patel HH, Roth DM (2010) Opioid-induced preconditioning is dependent on caveolin-3 expression. Anesth Analg 111:1117–1121. doi:10.1213/ANE.0b013e3181f3351a

    Article  PubMed  PubMed Central  Google Scholar 

  105. Tsutsumi YM, Tsutsumi R, Hamaguchi E, Sakai Y, Kasai A, Ishikawa Y, Yokoyama U, Tanaka K (2014) Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3. Cardiovasc Diabetol 13:132. doi:10.1186/s12933-014-0132-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Tsutsumi YM, Tsutsumi R, Horikawa YT, Sakai Y, Hamaguchi E, Ishikawa Y, Yokoyama U, Kasai A, Kambe N, Tanaka K (2014) Geranylgeranylacetone protects the heart via caveolae and caveolin-3. Life Sci 101:43–48. doi:10.1016/j.lfs.2014.02.019

    Article  CAS  PubMed  Google Scholar 

  107. Tsutsumi YM, Tsutsumi R, Horikawa YT, Sakai Y, Hamaguchi E, Kitahata H, Kasai A, Kambe N, Tanaka K (2014) Geranylgeranylacetone and volatile anesthetic-induced cardiac protection synergism is dependent on caveolae and caveolin-3. J Anesth 28:733–739. doi:10.1007/s00540-014-1816-8

    Article  PubMed  Google Scholar 

  108. Umegaki E, Kuramoto T, Kojima Y, Nouda S, Ishida K, Takeuchi T, Inoue T, Tokioka S, Higuchi K (2014) Geranylgeranylacetone, a gastromucoprotective drug, protects against NSAID-induced esophageal, gastroduodenal and small intestinal mucosal injury in healthy subjects: a prospective randomized study involving a comparison with famotidine. Intern Med 53:283–290. doi:10.2169/internalmedicine.53.1572

    Article  PubMed  CAS  Google Scholar 

  109. Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA (2006) Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114:2104–2112. doi:10.1161/circulationaha.106.635268

    Article  CAS  PubMed  Google Scholar 

  110. Volonte D, Galbiati F, Li S, Nishiyama K, Okamoto T, Lisanti MP (1999) Flotillins/cavatellins are differentially expressed in cells and tissues and form a hetero-oligomeric complex with caveolins in vivo. Characterization and epitope-mapping of a novel flotillin-1 monoclonal antibody probe. J Biol Chem 274:12702–12709. doi:10.1074/jbc.274.18.12702

    Article  CAS  PubMed  Google Scholar 

  111. Wang J, Schilling JM, Niesman IR, Headrick JP, Finley JC, Kwan E, Patel PM, Head BP, Roth DM, Yue Y, Patel HH (2014) Cardioprotective trafficking of caveolin to mitochondria is Gi-protein dependent. Anesthesiology 121:538–548. doi:10.1097/aln.0000000000000295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Wang X, Yuan B, Dong W, Yang B, Yang Y, Lin X, Gong G (2014) Induction of heat-shock protein 70 expression by geranylgeranylacetone shows cytoprotective effects in cardiomyocytes of mice under humid heat stress. PLoS One 9:e93536. doi:10.1371/journal.pone.0093536

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Wang Y, Wang X, Jasmin JF, Lau WB, Li R, Yuan Y, Yi W, Chuprun K, Lisanti MP, Koch WJ, Gao E, Ma XL (2012) Essential role of caveolin-3 in adiponectin signalsome formation and adiponectin cardioprotection. Arterioscler Thromb Vasc Biol 32:934–942. doi:10.1161/atvbaha.111.242164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Way M, Parton RG (1995) M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett 376:108–112. doi:10.1016/0014-5793(95)01256-7

    Article  CAS  PubMed  Google Scholar 

  115. Williams TM, Lisanti MP (2004) The caveolin proteins. Genome Biol 5:214. doi:10.1186/gb-2004-5-3-214

    Article  PubMed  PubMed Central  Google Scholar 

  116. Yang G, Dong Z, Xu H, Wang C, Li H, Li Z, Li F (2015) Structural study of caveolin-1 intramembrane domain by circular dichroism and nuclear magnetic resonance. Biopolymers 104:11–20. doi:10.1002/bip.22597

    Article  PubMed  CAS  Google Scholar 

  117. Yang Y, Duan W, Jin Z, Yi W, Yan J, Zhang S, Wang N, Liang Z, Li Y, Chen W, Yi D, Yu S (2013) JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury. J Pineal Res 55:275–286. doi:10.1111/jpi.12070

    Article  CAS  PubMed  Google Scholar 

  118. Yao Y, Hong S, Zhou H, Yuan T, Zeng R, Liao K (2009) The differential protein and lipid compositions of noncaveolar lipid microdomains and caveolae. Cell Res 19:497–506. doi:10.1038/cr.2009.27

    Article  CAS  PubMed  Google Scholar 

  119. Young LH, Ikeda Y, Lefer AM (2001) Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia–reperfusion via nitric oxide mechanism. Am J Physiol Heart Circ Physiol 280:H2489–H2495

    CAS  PubMed  Google Scholar 

  120. Yu H, Yang Z, Pan S, Yang Y, Tian J, Wang L, Sun W (2015) Hypoxic preconditioning promotes the translocation of protein kinase C epsilon binding with caveolin-3 at cell membrane not mitochondrial in rat heart. Cell Cycle 14:3557–3565. doi:10.1080/15384101.2015.1084446

    Article  CAS  PubMed  Google Scholar 

  121. Zhang J, Liem DA, Mueller M, Wang Y, Zong C, Deng N, Vondriska TM, Korge P, Drews O, Maclellan WR, Honda H, Weiss JN, Apweiler R, Ping P (2008) Altered proteome biology of cardiac mitochondria under stress conditions. J Proteome Res 7:2204–2214. doi:10.1021/pr070371f

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Zhang Y, Lv F, Jin L, Peng W, Song R, Ma J, Cao CM, Xiao RP (2011) MG53 participates in ischaemic postconditioning through the RISK signalling pathway. Cardiovasc Res 91:108–115. doi:10.1093/cvr/cvr029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Zhao J, Wang F, Zhang Y, Jiao L, Lau WB, Wang L, Liu B, Gao E, Koch WJ, Ma XL, Wang Y (2013) Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via caveolin-3-dependent cyclooxygenase-2 inhibition. Circulation 128:S121–S129. doi:10.1161/circulationaha.112.000045

    Article  CAS  PubMed  Google Scholar 

  124. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588. doi:10.1152/ajpheart.01064.2002

    Article  CAS  PubMed  Google Scholar 

  125. Zhu H, Hou J, Roe JL, Park KH, Tan T, Zheng Y, Li L, Zhang C, Liu J, Liu Z, Ma J, Walters TJ (2015) Amelioration of ischemia–reperfusion induced muscle injury by the recombinant human MG53 protein. Muscle Nerve 52:852–858. doi:10.1002/mus.24619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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    Authors and Affiliations

    1. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi’an, 710032, China

      Yang Yang & Wei Yi

    2. Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi’an, 710032, China

      Yang Yang & Wei Hu

    3. Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China

      Yang Yang & Dongjin Wang

    4. Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi’an, 710038, China

      Zhiqiang Ma, Chongxi Fan & Shouyin Di

    5. Department of Aerospace Medicine, The Fourth Military Medical University, Xi’an, 710032, China

      Shuai Jiang

    6. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 Beilishi Road, Beijing, 100037, China

      Dong Liu

    7. Department of Geriatrics, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi’an, 710032, China

      Yang Sun

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    Y. Yang and Z. Ma contributed equally to this work.

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    Yang, Y., Ma, Z., Hu, W. et al. Caveolin-1/-3: therapeutic targets for myocardial ischemia/reperfusion injury. Basic Res Cardiol 111, 45 (2016). https://doi.org/10.1007/s00395-016-0561-6

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