The Role of Adiponectin and Leptin in Fibro-Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Sep 28

PMID 39335491

Authors

Veronika A Myasoedova

Francesca Bertolini

Vincenza Valerio

Donato Moschetta

Ilaria Massaiu

Valentina Rusconi

Donato De Giorgi

Michele Ciccarelli

Valentina Parisi

Paolo Poggio

Affiliations

Soon will be listed here.

Abstract

Background: Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS).

Methods: A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger's test and funnel plots.

Results: Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = -0.143, 95% CI: -0.344, 0.057, = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: -0.045, 0.395, = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, = 0.025).

Conclusion: This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.

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References

Taneli F, Yegane S, Ulman C, Tikiz H, Bilge A, Ari Z . Increased serum leptin concentrations in patients with chronic stable angina pectoris and ST-elevated myocardial infarction. Angiology. 2006; 57(3):267-72. DOI: 10.1177/000331970605700302. View

Maffei M, Halaas J, Ravussin E, Pratley R, Lee G, Zhang Y . Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995; 1(11):1155-61. DOI: 10.1038/nm1195-1155. View

Mathieu P, Pibarot P, Despres J . Metabolic syndrome: the danger signal in atherosclerosis. Vasc Health Risk Manag. 2007; 2(3):285-302. PMC: 1993986. DOI: 10.2147/vhrm.2006.2.3.285. View

Rosa M, Paris C, Sottejeau Y, Corseaux D, Robin E, Tagzirt M . Leptin induces osteoblast differentiation of human valvular interstitial cells via the Akt and ERK pathways. Acta Diabetol. 2017; 54(6):551-560. DOI: 10.1007/s00592-017-0980-3. View

Singh P, Zhang Y, Sharma P, Covassin N, Soucek F, Friedman P . Statins decrease leptin expression in human white adipocytes. Physiol Rep. 2018; 6(2). PMC: 5789723. DOI: 10.14814/phy2.13566. View

Bodary P, Gu S, Shen Y, Hasty A, Buckler J, Eitzman D . Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005; 25(8):e119-22. DOI: 10.1161/01.ATV.0000173306.47722.ec. View

Considine R, Sinha M, Heiman M, Kriauciunas A, STEPHENS T, Nyce M . Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334(5):292-5. DOI: 10.1056/NEJM199602013340503. View

Lindman B, Clavel M, Mathieu P, Iung B, Lancellotti P, Otto C . Calcific aortic stenosis. Nat Rev Dis Primers. 2016; 2():16006. PMC: 5127286. DOI: 10.1038/nrdp.2016.6. View

Mick G, Wang X, Ling Fu C, McCORMICK K . Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue. Biochim Biophys Acta. 2000; 1502(3):426-32. DOI: 10.1016/s0925-4439(00)00074-0. View

10.

Singh P, Peterson T, Sert-Kuniyoshi F, Jensen M, Somers V . Leptin upregulates caveolin-1 expression: implications for development of atherosclerosis. Atherosclerosis. 2010; 217(2):499-502. PMC: 3482003. DOI: 10.1016/j.atherosclerosis.2010.10.012. View

11.

Patel J, Abraheem A, Dotsenko O, Creamer J, Gunning M, Hughes E . Circulating serum adiponectin levels in patients with coronary artery disease: relationship to atherosclerotic burden and cardiac function. J Intern Med. 2008; 264(6):593-8. DOI: 10.1111/j.1365-2796.2008.02007.x. View

12.

Martin S, Blaha M, Muse E, Qasim A, Reilly M, Blumenthal R . Leptin and incident cardiovascular disease: the Multi-ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2015; 239(1):67-72. PMC: 4331218. DOI: 10.1016/j.atherosclerosis.2014.12.033. View

13.

Minvielle Moncla L, Briend M, Bosse Y, Mathieu P . Calcific aortic valve disease: mechanisms, prevention and treatment. Nat Rev Cardiol. 2023; 20(8):546-559. DOI: 10.1038/s41569-023-00845-7. View

14.

Summerhill V, Moschetta D, Orekhov A, Poggio P, Myasoedova V . Sex-Specific Features of Calcific Aortic Valve Disease. Int J Mol Sci. 2020; 21(16). PMC: 7460640. DOI: 10.3390/ijms21165620. View

15.

Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z . Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol. 2011; 10:2. PMC: 3032658. DOI: 10.1186/1475-2840-10-2. View

16.

Lazzari P, Sanna A, Mastinu A, Cabasino S, Manca I, Pani L . Weight loss induced by rimonabant is associated with an altered leptin expression and hypothalamic leptin signaling in diet-induced obese mice. Behav Brain Res. 2010; 217(2):432-8. DOI: 10.1016/j.bbr.2010.11.022. View

17.

Cabuk G, Guray U, Kafes H, Guray Y, Cabuk A, Bayir P . Aortic valve sclerosis is associated with lower serum adiponectin levels. J Cardiovasc Med (Hagerstown). 2014; 16(6):451-5. DOI: 10.2459/JCM.0000000000000137. View

18.

Ouchi N, Walsh K . Adiponectin as an anti-inflammatory factor. Clin Chim Acta. 2007; 380(1-2):24-30. PMC: 2755046. DOI: 10.1016/j.cca.2007.01.026. View

19.

Mohty D, Pibarot P, Cote N, Cartier A, Audet A, Despres J . Hypoadiponectinemia is associated with valvular inflammation and faster disease progression in patients with aortic stenosis. Cardiology. 2011; 118(2):140-6. DOI: 10.1159/000327588. View

20.

Tam J, Cinar R, Liu J, Godlewski G, Wesley D, Jourdan T . Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab. 2012; 16(2):167-79. PMC: 3832894. DOI: 10.1016/j.cmet.2012.07.002. View