Skip to main content

Advertisement

SpringerLink
Log in

Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lourenco AP, Fontoura D, Henriques-Coelho T, Leite-Moreira AF (2012) Current pathophysiological concepts and management of pulmonary hypertension. Int J Cardiol 155:350–361. doi:10.1016/j.ijcard.2011.05.066

    Article  PubMed  Google Scholar 

  2. Uzum AK, Aydin MM, Tutuncu Y, Omer B, Kiyan E, Alagol F (2014) Serum ghrelin and adiponectin are increased but serum leptin level is unchanged in low weight patients. Chronic Obstr Pulm Dis 25:364–369. doi:10.1016/j.ejim.2013.02.012

    CAS  Google Scholar 

  3. Sumino H, Ichikawa S, Kasama S, Takahashi T, Sakamoto H, Kumakura H, Takayama Y, Kanda T, Murakami M, Kurabayashi M (2007) Relationship between brachial arterial endothelial function and lumbar spine bone mineral density in postmenopausal women. Circ J 71:1555–1559

    Article  CAS  PubMed  Google Scholar 

  4. Alangiakrishman K, Juby A, Hanley D, Tymchak W, Sclater A (2003) Role of vascular factors in osteoporosis. J Gerontoly Med Sci 58:362–366

    Article  Google Scholar 

  5. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M, Aboyans V, Vaz Carneiro A, Achenbach S, Agewall S, Allanore Y, Asteggiano R, Paolo Badano L, Albert Barberà J, Bouvaist H, Bueno H, Byrne RA, Carerj S, Castro G, Erol Ç, Falk V, Funck-Brentano C, Gorenflo M, Granton J, Iung B, Kiely DG, Kirchhof P, Kjellstrom B, Landmesser U, Lekakis J, Lionis C, Lip GY, Orfanos SE, Park MH, Piepoli MF, Ponikowski P, Revel MP, Rigau D, Rosenkranz S, Völler H, Luis Zamorano J (2016) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37:67–119. doi:10.1093/eurheartj/ehv317

    Article  PubMed  Google Scholar 

  6. Chemla D, Castelain V, Humbert M, Hébert JL, Simonneau G, Lecarpentier Y, Hervé P (2004) New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure. Chest 126:1313–1317. doi:10.1378/chest.126.4.1313

    Article  PubMed  Google Scholar 

  7. Tschopp O, Schmid C, Speich R, Seifert B, Russi EW, Boehler A (2006) Pretransplantation bone disease in patients with primary pulmonary hypertension. Chest 129:1002–1008. doi:10.1378/chest.129.4.1002

    Article  PubMed  Google Scholar 

  8. Malik N, McCarthy K, Minai OA (2012) Prevalence and significance of decreased bone density in pulmonary arterial hypertension. South Med J 105:344–349. doi:10.1097/SMJ.0b013e31825b8117

    Article  PubMed  Google Scholar 

  9. Nakanishi K, Takeda Y, Tetsumoto S, Iwasaki T, Tsujino K, Kuhara H, Jin Y, Nagatomo I, Kida H, Goya S, Kijima T, Maeda N, Funahashi T, Shimomura I, Tachibana I, Kawase I (2011) Involvement of endothelial apoptosis underlying chronic obstructive pulmonary disease-like phenotype in adiponectin-null mice. Implications for therapy. Am J Respir Crit Care Med 183:1164–1175. doi:10.1164/rccm.201007-1091OC

    Article  CAS  PubMed  Google Scholar 

  10. Vondracek SF, Voelkel NF, McDermott MT, Valdez C (2009) The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 4:267–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zheng Y, Ma A, Wang Q, Han X, Cai J, Schouten EG, Kok FJ, Li Y (2013) Relation of leptin, ghrelin and inflammatory cytokines with body mass index in pulmonary tuberculosis patients with and without type 2 diabetes mellitus. PLoS ONE 8(11):e80122. doi:10.1371/journal.pone.0080122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pobeha P, Ukropec J, Skyba P, Ukropcova B, Joppa P, Kurdiova T, Javorsky M, Klimes I, Tkac I, Gasperikova D, Tkacova R (2011) Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease. Bone 48(5):1008–1014. doi:10.1016/j.bone.2011.02.01.7

    Article  CAS  PubMed  Google Scholar 

  13. Summer R, Fiack CA, Ikeda Y, Sato K, Dwyer D, Ouchi N, Fine A, Farber HW, Walsh K (2009) Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease. Am J Physiol Lung Cell Mol Physiol 297:432–438. doi:10.1152/ajplung.90599.2008

    Article  Google Scholar 

  14. 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 112:1756–1762

    Article  CAS  PubMed  Google Scholar 

  15. Santos M, Reis A, Gonçalves F, Ferreira-Pinto MJ, Cabral S, Torres S, Leite-Moreira AF, Henriques-Coelho T (2014) Adiponectin levels are elevated in patients with pulmonary arterial hypertension. Clin Cardiol 37:21–25. doi:10.1002/clc.22210

    Article  PubMed  Google Scholar 

  16. Huertas A, Tu L, Gambaryan N, Girerd B, Perros F, Montani D, Fabre D, Fadel E, Eddahibi S, Cohen-Kaminsky S, Guignabert C, Humbert M (2012) Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension. Eur Respir J 40:895–904. doi:10.1183/09031936.00159911

    Article  CAS  PubMed  Google Scholar 

  17. Mohiti-Ardekani J, Soleymani-Salehabadi H, Owlia MB, Mohiti A (2014) Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients. J Bone Miner Metab 32:400–404. doi:10.1007/s00774-013-0511-4

    Article  CAS  PubMed  Google Scholar 

  18. Julia C, Czernichow S, Charnaux N, Ahluwalia N, Andreeva V, Touvier M, Galan P, Fezeu L (2014) Relationships between adipokines, biomarkers of endothelial function and inflammation and risk of type 2 diabetes. Diabetes Res Clin Pract 105:231–238. doi:10.1016/j.diabres.2014.05.001

    Article  CAS  PubMed  Google Scholar 

  19. Benza RL, Gomberg-Maitland M, Demarco T, Frost AE, Torbicki A, Langleben D, Pulido T, Correa-Jaque P, Passineau MJ, Wiener HW, Tamari M, Hirota T, Kubo M, Tiwari HK (2015) Endothelin-1 pathway polymorphisms and outcomes in pulmonary arterial hypertension. Am J Respir Crit Care Med 192:1345–1354. doi:10.1164/rccm.201501-0196OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Delgado-Frías E, López-Mejias R, Genre F, Ubilla B, Gómez Rodríguez-Bethencourt MA, González-Díaz A, de Vera-González AM, González-Rivero AF, Díaz-González F, González-Gay MA, Ferraz-Amaro I (2015) Relationship between endothelial dysfunction and osteoprotegerin, vitamin D, and bone mineral density in patients with rheumatoid arthritis. Clin Exp Rheumatol 33:241–249

    PubMed  Google Scholar 

  21. Serizawa K, Yogo K, Tashiro Y, Takeda S, Kawasaki R, Aizawa K, Endo K (2016) Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats. J Endocrinol 228:75–84. doi:10.1530/JOE-15-0332

    Article  CAS  PubMed  Google Scholar 

  22. Mestek ML, Weil BR, Greiner JJ, Westby CM, DeSouza CA, Stauffer BL (2010) Osteopenia and endothelin-1-mediated vasconstrictor tone in postmenopausal women. Bone 47:542–545. doi:10.1016/j.bone.2010.05.041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Prasad M, Reriani M, Khosla S, Gössl M, Lennon R, Gulati R, Prasad A, Lerman LO, Lerman A (2014) Coronary microvascular endothelial dysfunction is an independent predictor of development of osteoporosis in postmenopausal women. Vasc Health Risk Manag 26:533–538. doi:10.2147/VHRM.S63580

    Google Scholar 

  24. Madonna R, Novo G, Balistreri CR (2016) Cellular and molecular basis of the imbalance between vascular damage and repair in ageing and age-related diseases: as biomarkers and targets for new treatments. Mech Ageing Dev 159:22-30. doi:10.1016/j.mad.2016.03.005

    Article  CAS  PubMed  Google Scholar 

  25. Funada Y, Nishimura Y, Youkoyama M (2004) Imbalance of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 is associated with pulmonary emphysema in Klotho mice. Kobe J Med Sci 50:59–67

    CAS  PubMed  Google Scholar 

  26. Withers SB, Bussey CE, Saxton SN, Melrose HM, Watkins AE, Heagerty AM (2014) Mechanisms of adiponectin-associated perivascular function in vascular disease. Arterioscler Thromb Vasc Biol 34:1637–1642. doi:10.1161/ATVBAHA.114.303031

    Article  CAS  PubMed  Google Scholar 

  27. Oda A, Taniguchi T, Yokoyama M (2001) Leptin stimulates rat aortic smooth muscle cell proliferation and migration. Kobe J Med Sci 47:141–150

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from Russian Science Foundation (No. 14-33-00009). The study sponsors had no role in study design, data collection, data analysis, data interpretation and/or writing of the report. We are very grateful to Christa Burdick (University of Massachusetts Amherst, USA) for her thoughtful revision of this article.

Authors’ Contribution

EAK and VAN designed the study. LGU, YuVM, EAK were involved in patient selection and sample collection. EAK, LGU carried out the laboratory work. EAK, VAN, YuVM did the data analysis. EAK, VAN worked on interpretation of the data and writing and the manuscript. All authors revised the paper critically for intellectual content and approved the final version. EAK is the guarantor of the paper. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Author information

Authors and Affiliations

  1. Central Scientific Research Laboratory, Pacific State Medical University, Vladivostok, Russian Federation

    Evgenia A. Kochetkova, Ludmila G. Ugai, Yuliya V. Maistrovskaia & Vera A. Nevzorova

  2. Department of Pulmonology, Pacific State Medical University, 2 Ostryakova Av., Vladivostok, Russian Federation, 690950

    Evgenia A. Kochetkova

Authors
  1. Evgenia A. Kochetkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ludmila G. Ugai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuliya V. Maistrovskaia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vera A. Nevzorova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evgenia A. Kochetkova.

Ethics declarations

Conflicts of interest

Evgenia A. Kochetkova, Vera A. Nevzorova, Ludmila G. Ugai, and Yulia V. Maistrovskaia declare that they have no conflict of interest.

Human and Animal Rights Statement

All procedures involving human subjects were approved by the local Human Investigation ethics committee.

Informed Consent Statement

Written informed consent was obtained from all subjects.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kochetkova, E.A., Ugai, L.G., Maistrovskaia, Y.V. et al. Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension. Calcif Tissue Int 100, 325–331 (2017). https://doi.org/10.1007/s00223-016-0224-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-016-0224-5

Keywords

Search

Navigation