The evolving role of adiponectin as an additive biomarker in HFrEF

Heart Failure Reviews

Volumn 21, Issue 6, 2016, Pages 753-769

  Sente, Tahnee ^a,b   Gevaert, Andreas ^a,b   Van Berendoncks, An ^b   Vrints, Christiaan J ^a,b   Hoymans, Vicky Y ^a,b  

^a ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Adiponectin; Biomarker; Cardioprotection; Heart failure; Inflammation

Indexed keywords

ADIPONECTIN; ADIPONECTIN RECEPTOR; BIOLOGICAL MARKER; BRAIN NATRIURETIC PEPTIDE; TUMOR NECROSIS FACTOR;

ANTIINFLAMMATORY ACTIVITY; AORTA CONSTRICTION; ARTICLE; BIOLOGICAL ACTIVITY; HEART BLOOD VESSEL; HEART EJECTION FRACTION; HEART FAILURE; HEART PROTECTION; HUMAN; NONHUMAN; PROGNOSIS; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; RISK REDUCTION; BLOOD; CHRONIC DISEASE; DISEASE EXACERBATION; HEART STROKE VOLUME; PATHOPHYSIOLOGY; PHYSIOLOGY; RISK FACTOR;

ADIPONECTIN; BIOMARKERS; CHRONIC DISEASE; DISEASE PROGRESSION; HEART FAILURE; HUMANS; PROGNOSIS; RISK FACTORS; STROKE VOLUME;

EID: 84982803799     PISSN: 13824147     EISSN: 15737322     Source Type: Journal    
DOI: 10.1007/s10741-016-9578-z     Document Type: Article

References (131)

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J, American Heart Association Statistics C, Stroke Statistics S (2010) Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121(7):948–954. doi:10.1161/CIRCULATIONAHA.109.192666
2. Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, Roger VL (2006) Systolic and diastolic heart failure in the community. JAMA 296(18):2209–2216. doi:10.1001/jama.296.18.2209
3. Bui AL, Horwich TB, Fonarow GC (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8(1):30–41. doi:10.1038/nrcardio.2010.165
4. Warriner D, Sheridan P, Lawford P (2015) Heart failure: not a single organ disease but a multisystem syndrome. Br J Hosp Med 76(6):330–336. doi:10.12968/hmed.2015.76.6.330
5. Joosten MM, Joshipura KJ, Pai JK, Bertoia ML, Rimm EB, Mittleman MA, Mukamal KJ (2013) Total adiponectin and risk of symptomatic lower extremity peripheral artery disease in men. Arterioscler Thromb Vasc Biol 33(5):1092–1097. doi:10.1161/ATVBAHA.112.301089
6. Sook Lee E, Park SS, Kim E, Sook Yoon Y, Ahn HY, Park CY, Ho Yun Y, Woo OhS (2013) Association between adiponectin levels and coronary heart disease and mortality: a systematic review and meta-analysis. Int J Epidemiol 42(4):1029–1039. doi:10.1093/ije/dyt087
7. Shibata R, Ouchi N, Murohara T (2009) Adiponectin and cardiovascular disease. Circ J 73(4):608–614
8. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102(11):1296–1301
9. Ouedraogo R, Wu X, Xu SQ, Fuchsel L, Motoshima H, Mahadev K, Hough K, Scalia R, Goldstein BJ (2006) Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes 55(6):1840–1846. doi:10.2337/db05-1174
10. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, Lopez BL, Koch W, Chan L, Goldstein BJ, Ma XL (2007) Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115(11):1408–1416. doi:10.1161/CIRCULATIONAHA.106.666941
11. Frystyk J, Berne C, Berglund L, Jensevik K, Flyvbjerg A, Zethelius B (2007) Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men. J Clin Endocrinol Metab 92(2):571–576. doi:10.1210/jc.2006-1067
12. Haugen E, Furukawa Y, Isic A, Fu M (2008) Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: a hospital cohort study. Int J Cardiol 125(2):216–219. doi:10.1016/j.ijcard.2007.12.002
13. Nakamura T, Funayama H, Kubo N, Yasu T, Kawakami M, Saito M, Momomura S, Ishikawa SE (2006) Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure. Circ J 70(12):1557–1562
14. Sokhanvar S, Sheykhi M, Mazlomzade S, Taran L, Golmohammadi Z (2013) The relationship between serum adiponectin and prognosis in patients with heart failure. Bratisl Lek Listy 114(8):455–459
15. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270(45):26746–26749
16. Shapiro L, Scherer PE (1998) The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 8(6):335–338
17. Fang X, Sweeney G (2006) Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem Soc Trans 34(Pt 5):798–801. doi:10.1042/BST0340798
18. Yamauchi T, Kadowaki T (2008) Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes 32(Suppl 7):S13–S18. doi:10.1038/ijo.2008.233
19. Tsao TS, Tomas E, Murrey HE, Hug C, Lee DH, Ruderman NB, Heuser JE, Lodish HF (2003) Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem 278(50):50810–50817. doi:10.1074/jbc.M309469200
20. Waki H, Yamauchi T, Kamon J, Kita S, Ito Y, Hada Y, Uchida S, Tsuchida A, Takekawa S, Kadowaki T (2005) Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 146(2):790–796. doi:10.1210/en.2004-1096
21. Aso Y, Yamamoto R, Wakabayashi S, Uchida T, Takayanagi K, Takebayashi K, Okuno T, Inoue T, Node K, Tobe T, Inukai T, Nakano Y (2006) Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. Diabetes 55(7):1954–1960. doi:10.2337/db05-1525
22. Fisher FM, Trujillo ME, Hanif W, Barnett AH, McTernan PG, Scherer PE, Kumar S (2005) Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia 48(6):1084–1087. doi:10.1007/s00125-005-1758-7
23. Nanayakkara G, Kariharan T, Wang L, Zhong J, Amin R (2012) The cardio-protective signaling and mechanisms of adiponectin. Am J Cardiovasc Dis 2(4):253–266
24. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, Wagner JA, Wu M, Knopps A, Xiang AH, Utzschneider KM, Kahn SE, Olefsky JM, Buchanan TA, Scherer PE (2004) Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 279(13):12152–12162. doi:10.1074/jbc.M311113200
25. Heidemann C, Sun Q, van Dam RM, Meigs JB, Zhang C, Tworoger SS, Mantzoros CS, Hu FB (2008) Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med 149(5):307–316
26. Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS, Scherer PE (2003) Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 52(2):268–276
27. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y (2002) Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51(9):2734–2741
28. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G (2003) Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 52(7):1779–1785
29. Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35(4):842–849. doi:10.1016/j.bone.2004.06.008
30. Delaigle AM, Jonas JC, Bauche IB, Cornu O, Brichard SM (2004) Induction of adiponectin in skeletal muscle by inflammatory cytokines: in vivo and in vitro studies. Endocrinology 145(12):5589–5597. doi:10.1210/en.2004-0503
31. Krause MP, Liu Y, Vu V, Chan L, Xu A, Riddell MC, Sweeney G, Hawke TJ (2008) Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. Am J Physiol Cell Physiol 295(1):C203–C212. doi:10.1152/ajpcell.00030.2008
32. Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26(3):439–451. doi:10.1210/er.2005-0005
33. Ouchi N, Walsh K (2007) Adiponectin as an anti-inflammatory factor. Clin Chim Acta 380(1–2):24–30. doi:10.1016/j.cca.2007.01.026
34. Shinmura K (2010) Is adiponectin a bystander or a mediator in heart failure? the tangled thread of a good-natured adipokine in aging and cardiovascular disease. Heart Fail Rev 15(5):457–466. doi:10.1007/s10741-010-9159-5
35. Tsubakio-Yamamoto K, Matsuura F, Koseki M, Oku H, Sandoval JC, Inagaki M, Nakatani K, Nakaoka H, Kawase R, Yuasa-Kawase M, Masuda D, Ohama T, Maeda N, Nakagawa-Toyama Y, Ishigami M, Nishida M, Kihara S, Shimomura I, Yamashita S (2008) Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem Biophys Res Commun 375(3):390–394. doi:10.1016/j.bbrc.2008.08.009
36. Karbowska J, Kochan Z (2006) Role of adiponectin in the regulation of carbohydrate and lipid metabolism. J Physiol Pharmacol 57(Suppl 6):103–113
37. Shibata R, Skurk C, Ouchi N, Galasso G, Kondo K, Ohashi T, Shimano M, Kihara S, Murohara T, Walsh K (2008) Adiponectin promotes endothelial progenitor cell number and function. FEBS Lett 582(11):1607–1612. doi:10.1016/j.febslet.2008.04.006
38. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423(6941):762–769. doi:10.1038/nature01705
39. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13(3):332–339. doi:10.1038/nm1557
40. Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T (2014) Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 28(1):15–23. doi:10.1016/j.beem.2013.09.003
41. Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, Motoyama K, Ikeda M, Wakiyama M, Terada T, Ohsawa N, Hato M, Ogasawara S, Hino T, Murata T, Iwata S, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Shirouzu M, Yamauchi T, Kadowaki T, Yokoyama S (2015) Crystal structures of the human adiponectin receptors. Nature 520(7547):312–316. doi:10.1038/nature14301
42. Yamaguchi N, Argueta JG, Masuhiro Y, Kagishita M, Nonaka K, Saito T, Hanazawa S, Yamashita Y (2005) Adiponectin inhibits Toll-like receptor family-induced signaling. FEBS Lett 579(30):6821–6826. doi:10.1016/j.febslet.2005.11.019
43. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8(11):1288–1295. doi:10.1038/nm788
44. Yoon MJ, Lee GY, Chung JJ, Ahn YH, Hong SH, Kim JB (2006) Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes 55(9):2562–2570. doi:10.2337/db05-1322
45. Cheng KK, Lam KS, Wang Y, Huang Y, Carling D, Wu D, Wong C, Xu A (2007) Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. Diabetes 56(5):1387–1394. doi:10.2337/db06-1580
46. Mao X, Kikani CK, Riojas RA, Langlais P, Wang L, Ramos FJ, Fang Q, Christ-Roberts CY, Hong JY, Kim RY, Liu F, Dong LQ (2006) APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol 8(5):516–523. doi:10.1038/ncb1404
47. Deepa SS, Dong LQ (2009) APPL1: role in adiponectin signaling and beyond. Am J Physiol Endocrinol Metab 296(1):E22–E36. doi:10.1152/ajpendo.90731.2008
48. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF (2004) T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA 101(28):10308–10313. doi:10.1073/pnas.0403382101
49. Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B (2010) T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Investig 120(12):4342–4352. doi:10.1172/JCI43464
50. Motoshima H, Wu X, Mahadev K, Goldstein BJ (2004) Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 315(2):264–271. doi:10.1016/j.bbrc.2004.01.049
51. Tao L, Wang Y, Gao E, Zhang H, Yuan Y, Lau WB, Chan L, Koch WJ, Ma XL (2010) Adiponectin: an indispensable molecule in rosiglitazone cardioprotection following myocardial infarction. Circ Res 106(2):409–417. doi:10.1161/CIRCRESAHA.109.211797
52. Goldstein BJ, Scalia RG, Ma XL (2009) Protective vascular and myocardial effects of adiponectin. Nat Clin Pract Cardiovasc Med 6(1):27–35. doi:10.1038/ncpcardio1398
53. Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A (2008) Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci 114(5):361–374. doi:10.1042/CS20070347
54. Jahng JW, Turdi S, Kovacevic V, Dadson K, Li RK, Sweeney G (2015) Pressure overload-induced cardiac dysfunction in aged male adiponectin knockout mice is associated with autophagy deficiency. Endocrinology 156(7):2667–2677. doi:10.1210/en.2015-1162
55. Liao Y, Takashima S, Maeda N, Ouchi N, Komamura K, Shimomura I, Hori M, Matsuzawa Y, Funahashi T, Kitakaze M (2005) Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res 67(4):705–713. doi:10.1016/j.cardiores.2005.04.018
56. O’Shea KM, Chess DJ, Khairallah RJ, Rastogi S, Hecker PA, Sabbah HN, Walsh K, Stanley WC (2010) Effects of adiponectin deficiency on structural and metabolic remodeling in mice subjected to pressure overload. Am J Physiol Heart Circ Physiol 298(6):H1639–H1645. doi:10.1152/ajpheart.00957.2009
57. Shimano M, Ouchi N, Shibata R, Ohashi K, Pimentel DR, Murohara T, Walsh K (2010) Adiponectin deficiency exacerbates cardiac dysfunction following pressure overload through disruption of an AMPK-dependent angiogenic response. J Mol Cell Cardiol 49(2):210–220. doi:10.1016/j.yjmcc.2010.02.021
58. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y (2002) Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106(22):2767–2770
59. Kato H, Kashiwagi H, Shiraga M, Tadokoro S, Kamae T, Ujiie H, Honda S, Miyata S, Ijiri Y, Yamamoto J, Maeda N, Funahashi T, Kurata Y, Shimomura I, Tomiyama Y, Kanakura Y (2006) Adiponectin acts as an endogenous antithrombotic factor. Arterioscler Thromb Vasc Biol 26(1):224–230. doi:10.1161/01.ATV.0000194076.84568.81
60. Kondo K, Shibata R, Unno K, Shimano M, Ishii M, Kito T, Shintani S, Walsh K, Ouchi N, Murohara T (2010) Impact of a single intracoronary administration of adiponectin on myocardial ischemia/reperfusion injury in a pig model. Circ Cardiovasc Intervent 3(2):166–173. doi:10.1161/CIRCINTERVENTIONS.109.872044
61. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K (2005) Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 11(10):1096–1103. doi:10.1038/nm1295
62. Kojima S, Kojima S, Maruyoshi H, Nagayoshi Y, Kaikita K, Sumida H, Sugiyama S, Funahashi T, Ogawa H (2011) Hypercholesterolemia and hypoadiponectinemia are associated with necrotic core-rich coronary plaque. Int J Cardiol 147(3):371–376. doi:10.1016/j.ijcard.2009.09.536
63. Sawada T, Shite J, Shinke T, Otake H, Tanino Y, Ogasawara D, Kawamori H, Kato H, Miyoshi N, Yoshino N, Kozuki A, Hirata K (2010) Low plasma adiponectin levels are associated with presence of thin-cap fibroatheroma in men with stable coronary artery disease. Int J Cardiol 142(3):250–256. doi:10.1016/j.ijcard.2008.12.216
64. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y (2002) Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 277(40):37487–37491. doi:10.1074/jbc.M206083200
65. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T (2003) Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 278(4):2461–2468. doi:10.1074/jbc.M209033200
66. Xu A, Wang Y, Lam KS, Vanhoutte PM (2010) Vascular actions of adipokines molecular mechanisms and therapeutic implications. Adv Pharmacol 60:229–255. doi:10.1016/B978-0-12-385061-4.00008-8
67. Ohashi K, Ouchi N, Sato K, Higuchi A, Ishikawa TO, Herschman HR, Kihara S, Walsh K (2009) Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism. Mol Cell Biol 29(13):3487–3499. doi:10.1128/MCB.00126-09
68. Joshi MB, Philippova M, Ivanov D, Allenspach R, Erne P, Resink TJ (2005) T-cadherin protects endothelial cells from oxidative stress-induced apoptosis. FASEB J 19(12):1737–1739. doi:10.1096/fj.05-3834fje
69. George J, Patal S, Wexler D, Sharabi Y, Peleg E, Kamari Y, Grossman E, Sheps D, Keren G, Roth A (2006) Circulating adiponectin concentrations in patients with congestive heart failure. Heart 92(10):1420–1424. doi:10.1136/hrt.2005.083345
70. Hopkins TA, Ouchi N, Shibata R, Walsh K (2007) Adiponectin actions in the cardiovascular system. Cardiovasc Res 74(1):11–18. doi:10.1016/j.cardiores.2006.10.009
71. Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, Hildebrandt P (2005) Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 112(12):1756–1762. doi:10.1161/CIRCULATIONAHA.104.530972
72. Tsutamoto T, Tanaka T, Sakai H, Ishikawa C, Fujii M, Yamamoto T, Horie M (2007) Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure. Eur Heart J 28(14):1723–1730. doi:10.1093/eurheartj/ehm154
73. Norrelund H, Wiggers H, Halbirk M, Frystyk J, Flyvbjerg A, Botker HE, Schmitz O, Jorgensen JO, Christiansen JS, Moller N (2006) Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure. J Intern Med 260(1):11–21. doi:10.1111/j.1365-2796.2006.01663.x
74. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM (2010) Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail 3(2):185–194. doi:10.1161/CIRCHEARTFAILURE.109.885525
75. Beatty AL, Zhang MH, Ku IA, Na B, Schiller NB, Whooley MA (2012) Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study. Atherosclerosis 220(2):587–592. doi:10.1016/j.atherosclerosis.2011.11.038
76. Baldasseroni S, Mannucci E, Orso F, Di Serio C, Pratesi A, Bartoli N, Marella GA, Colombi C, Foschini A, Valoti P, Mossello E, Fumagalli S, Marchionni N, Tarantini F (2012) Adiponectin in outpatients with coronary artery disease: independent predictors and relationship with heart failure. Nutr Metab Cardiovasc Dis 22(3):292–299. doi:10.1016/j.numecd.2011.03.012
77. Ohara T, Hashimura K, Asakura M, Ogai A, Amaki M, Hasegawa T, Kanzaki H, Sonoda M, Nishizawa H, Funahashi T, Kitakaze M (2011) Dynamic changes in plasma total and high molecular weight adiponectin levels in acute heart failure. J Cardiol 58(2):181–190. doi:10.1016/j.jjcc.2011.06.010
78. Gustafsson S, Lind L, Zethelius B, Venge P, Flyvbjerg A, Soderberg S, Ingelsson E (2010) Adiponectin and cardiac geometry and function in elderly: results from two community-based cohort studies. Eur J Endocrinol 162(3):543–550. doi:10.1530/EJE-09-1006
79. Kung T, Szabo T, Springer J, Doehner W, Anker SD, von Haehling S (2011) Cachexia in heart disease: highlights from the ESC 2010. J Cachexia Sarcopenia Muscle 2(1):63–69. doi:10.1007/s13539-011-0020-z
80. Lee Y, Kim BK, Lim YH, Kim MK, Choi BY, Shin J (2013) The relationship between adiponectin and left ventricular mass index varies with the risk of left ventricular hypertrophy. PLoS ONE 8(7):e70246. doi:10.1371/journal.pone.0070246
81. Sam F, Walsh K (2010) What can adiponectin say about left ventricular function? Heart 96(5):331–332. doi:10.1136/hrt.2009.178590
82. Ebert T, Fasshauer M (2011) Adiponectin: sometimes good, sometimes bad? Cardiology 118(4):236–237. doi:10.1159/000329647
83. Sente T, Van Berendoncks AM, Hoymans VY, Vrints CJ (2015) Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure. J Cachexia Sarcopenia Muscle. doi:10.1002/jcsm.12086
84. Hashimoto N, Kanda J, Nakamura T, Horie A, Kurosawa H, Hashimoto T, Sato K, Kushida S, Suzuki M, Yano S, Iwai R, Takahashi H, Yoshida S (2006) Association of hypoadiponectinemia in men with early onset of coronary heart disease and multiple coronary artery stenoses. Metab, Clin Exp 55(12):1653–1657. doi:10.1016/j.metabol.2006.08.005
85. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T (2004) Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 43(6):1318–1323. doi:10.1161/01.HYP.0000129281.03801.4b
86. Lindberg S, Pedersen SH, Mogelvang R, Bjerre M, Frystyk J, Flyvbjerg A, Galatius S, Jensen JS (2012) Usefulness of adiponectin as a predictor of all cause mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Am J Cardiol 109(4):492–496. doi:10.1016/j.amjcard.2011.09.041
87. Won H, Kang SM, Shin MJ, Oh J, Hong N, Park S, Lee SH, Jang Y, Chung N (2012) Plasma adiponectin concentration and its association with metabolic syndrome in patients with heart failure. Yonsei Med J 53(1):91–98. doi:10.3349/ymj.2012.53.1.91
88. Li S, Shin HJ, Ding EL, van Dam RM (2009) Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 302(2):179–188. doi:10.1001/jama.2009.976
89. Okamoto H (2009) Can adiponectin be a novel metabolic biomarker for heart failure? Circ J 73(6):1012–1013
90. Yamaji M, Tsutamoto T, Tanaka T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, Horie M (2009) Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure. Circ J 73(6):1067–1073
91. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB (2004) Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730–1737. doi:10.1001/jama.291.14.1730
92. Kawano T, Saito T, Yasu T, Saito T, Nakamura T, Namai K, Tamemoto H, Kawakami M, Saito M, Ishikawa SE (2005) Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease. Metab, Clin Exp 54(5):653–656. doi:10.1016/j.metabol.2004.12.009
93. Djousse L, Wilk JB, Hanson NQ, Glynn RJ, Tsai MY, Gaziano JM (2013) Association between adiponectin and heart failure risk in the physicians’ health study. Obesity 21(4):831–834. doi:10.1002/oby.20260
94. Shibata R, Izumiya Y, Sato K, Papanicolaou K, Kihara S, Colucci WS, Sam F, Ouchi N, Walsh K (2007) Adiponectin protects against the development of systolic dysfunction following myocardial infarction. J Mol Cell Cardiol 42(6):1065–1074. doi:10.1016/j.yjmcc.2007.03.808
95. Kizer JR, Arnold AM, Jenny NS, Cushman M, Strotmeyer ES, Ives DG, Ding J, Kritchevsky SB, Chaves PH, Hirsch CH, Newman AB (2011) Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study. J Gerontol A Biol Sci Med Sci 66(10):1100–1107. doi:10.1093/gerona/glr098
96. Kizer JR, Benkeser D, Arnold AM, Mukamal KJ, Ix JH, Zieman SJ, Siscovick DS, Tracy RP, Mantzoros CS, Defilippi CR, Newman AB, Djousse L (2012) Associations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study. Circulation 126(25):2951–2961. doi:10.1161/CIRCULATIONAHA.112.135202
97. Macheret F, Bartz TM, Djousse L, Ix JH, Mukamal KJ, Zieman SJ, Siscovick DS, Tracy RP, Heckbert SR, Psaty BM, Kizer JR (2015) Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults. Heart 101(17):1368–1374. doi:10.1136/heartjnl-2014-307015
98. Kizer JR, Arnold AM, Benkeser D, Ix JH, Djousse L, Zieman SJ, Barzilay JI, Tracy RP, Mantzoros CS, Siscovick DS, Mukamal KJ (2012) Total and high-molecular-weight adiponectin and risk of incident diabetes in older people. Diabetes Care 35(2):415–423. doi:10.2337/dc11-1519
99. Park M, Sweeney G (2013) Direct effects of adipokines on the heart: focus on adiponectin. Heart Fail Rev 18(5):631–644. doi:10.1007/s10741-012-9337-8
100. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100(25):2473–2476
101. Pineiro R, Iglesias MJ, Gallego R, Raghay K, Eiras S, Rubio J, Dieguez C, Gualillo O, Gonzalez-Juanatey JR, Lago F (2005) Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett 579(23):5163–5169. doi:10.1016/j.febslet.2005.07.098
102. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96(5):1723–1732
103. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, Okamoto Y, Ohashi K, Nagaretani H, Kishida K, Nishizawa H, Maeda N, Kobayashi H, Hiraoka H, Matsuzawa Y (2003) Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 107(5):671–674
104. Devaraj S, Torok N, Dasu MR, Samols D, Jialal I (2008) Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells: evidence for an adipose tissue-vascular loop. Arterioscler Thromb Vasc Biol 28(7):1368–1374. doi:10.1161/ATVBAHA.108.163303
105. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE (2011) Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 17(1):55–63. doi:10.1038/nm.2277
106. Essick EE, Wilson RM, Pimentel DR, Shimano M, Baid S, Ouchi N, Sam F (2013) Adiponectin modulates oxidative stress-induced autophagy in cardiomyocytes. PLoS ONE 8(7):e68697. doi:10.1371/journal.pone.0068697
107. Park M, Youn B, Zheng XL, Wu D, Xu A, Sweeney G (2011) Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PLoS ONE 6(4):e19143. doi:10.1371/journal.pone.0019143
108. Tsatsanis C, Zacharioudaki V, Androulidaki A, Dermitzaki E, Charalampopoulos I, Minas V, Gravanis A, Margioris AN (2005) Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun 335(4):1254–1263. doi:10.1016/j.bbrc.2005.07.197
109. Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2(12):965–975. doi:10.1038/nri957
110. Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, Kihara S, Walsh K (2007) Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Investig 117(2):375–386. doi:10.1172/JCI29709
111. Fantuzzi G (2008) Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol 121(2):326–330. doi:10.1016/j.jaci.2007.10.018
112. Tomizawa A, Hattori Y, Kasai K (2009) Induction of gene expression in response to globular adiponectin in vascular endothelial cells. Life Sci 85(11–12):457–461. doi:10.1016/j.lfs.2009.07.012
113. Ehling A, Schaffler A, Herfarth H, Tarner IH, Anders S, Distler O, Paul G, Distler J, Gay S, Scholmerich J, Neumann E, Muller-Ladner U (2006) The potential of adiponectin in driving arthritis. J Immunol 176(7):4468–4478
114. Heliovaara MK, Teppo AM, Karonen SL, Tuominen JA, Ebeling P (2006) Improved glycaemia in type 1 diabetes results in decreased levels of soluble adhesion molecules with no change in serum adiponectin or most acute phase proteins. Exp Clin Endocrinol Diabetes 114(6):295–300. doi:10.1055/s-2006-924265
115. Kirdar S, Serter M, Ceylan E, Sener AG, Kavak T, Karadag F (2009) Adiponectin as a biomarker of systemic inflammatory response in smoker patients with stable and exacerbation phases of chronic obstructive pulmonary disease. Scand J Clin Lab Invest 69(2):219–224. doi:10.1080/00365510802474400
116. Miller M, Pham A, Cho JY, Rosenthal P, Broide DH (2010) Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema. Am J Physiol Lung Cell Mol Physiol 299(6):L834–L842. doi:10.1152/ajplung.00326.2009
117. Ho YL, Lin YH, Lee CM, Hsu RB, Ting HT, Chou NK, Chao CL, Wang SS, Hsu HC, Chen MF (2009) Prognostic significance of adipocytokines and extracellular matrix activity in heart failure patients with high B-type natriuretic peptide. Clin Biochem 42(13–14):1407–1412. doi:10.1016/j.clinbiochem.2009.06.013
118. + T cells. J Biol Chem 287(44):36896–36904. doi:10.1074/jbc.M112.409516
119. Park PH, McMullen MR, Huang H, Thakur V, Nagy LE (2007) Short-term treatment of RAW264.7 macrophages with adiponectin increases tumor necrosis factor-alpha (TNF-alpha) expression via ERK1/2 activation and Egr-1 expression: role of TNF-alpha in adiponectin-stimulated interleukin-10 production. J Biol Chem 282(30):21695–21703. doi:10.1074/jbc.M701419200
120. Cavusoglu E, Chopra V, Battala V, Ruwende C, Yanamadala S, Eng C, Pinsky DJ, Marmur JD (2008) Baseline plasma adiponectin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography. Am J Cardiol 101(8):1073–1078. doi:10.1016/j.amjcard.2007.12.008
121. Celik T, Yaman H (2010) Elevated adiponectin levels in patients with chronic heart failure: an independent predictor of mortality or a marker of cardiac cachexia? Int J Cardiol 144(2):319–320. doi:10.1016/j.ijcard.2009.03.006
122. Dieplinger B, Gegenhuber A, Poelz W, Haltmayer M, Mueller T (2009) Prognostic value of increased adiponectin plasma concentrations in patients with acute destabilized heart failure. Clin Biochem 42(10–11):1190–1193. doi:10.1016/j.clinbiochem.2009.02.023
123. Adamopoulos S, Coats AJ, Brunotte F, Arnolda L, Meyer T, Thompson CH, Dunn JF, Stratton J, Kemp GJ, Radda GK et al (1993) Physical training improves skeletal muscle metabolism in patients with chronic heart failure. J Am Coll Cardiol 21(5):1101–1106
124. Van Berendoncks AM, Beckers P, Hoymans VY, Possemiers N, Coenen S, Elseviers MM, Vrints CJ, Conraads VM (2011) beta-blockers modify the prognostic value of adiponectin in chronic heart failure. Int J Cardiol 150(3):296–300. doi:10.1016/j.ijcard.2010.04.039
125. Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, Shimamoto K (2005) Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol 153(1):91–98. doi:10.1530/eje.1.01930
126. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Van Hoof V, Dewilde S, Vrints CJ, Ventura-Clapier R, Conraads VM (2011) Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure. Heart 97(17):1403–1409. doi:10.1136/hrt.2011.226373
127. Dieplinger B, Gegenhuber A, Haltmayer M, Mueller T (2009) Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath. Heart 95(18):1508–1513. doi:10.1136/hrt.2009.170696
128. Fu M, Zhou J, Qian J, Jin X, Zhu H, Zhong C, Fu M, Zou Y, Ge J (2012) Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction—an experimental study. Lipids Health Dis 11:106. doi:10.1186/1476-511X-11-106
129. Risch L, Saely C, Hoefle G, Rein P, Langer P, Gouya G, Marte T, Aczel S, Drexel H (2007) Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function. Clin Chim Acta 376(1–2):108–113. doi:10.1016/j.cca.2006.07.026
130. Tentolouris N, Doulgerakis D, Moyssakis I, Kyriaki D, Makrilakis K, Kosmadakis G, Stamatiadis D, Katsilambros N, Stathakis C (2004) Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease. Horm Metab Res 36(10):721–727. doi:10.1055/s-2004-826022
131. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y (2002) Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13(1):134–141