Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 19

PMID 23596511

Citations 21

Authors

Zoltan Prohaszka

Lea Munthe-Fog

Thor Ueland

Timea Gombos

Arne Yndestad

Zsolt Forhecz

Mikkel-Ole Skjoedt

Zoltan Pozsonyi

Alice Gustavsen

Livia Janoskuti

Istvan Karadi

Lars Gullestad

Christen P Dahl

Erik T Askevold

George Fust

Pal Aukrust

Tom E Mollnes

Peter Garred

Affiliations

Soon will be listed here.

Abstract

Background: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.

Methods And Results: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.

Conclusions: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.

Citing Articles

Uncovering hub genes and immunological characteristics for heart failure utilizing RRA, WGCNA and Machine learning.

Tu D, Xu Q, Zuo X, Ma C Int J Cardiol Heart Vasc. 2024; 51:101335.

PMID: 38371312 PMC: 10869931. DOI: 10.1016/j.ijcha.2024.101335.

Identification of Co-diagnostic Genes for Heart Failure and Hepatocellular Carcinoma Through WGCNA and Machine Learning Algorithms.

Cao L, Wang X, Li X, Ma L, Li Y Mol Biotechnol. 2024; 66(5):1229-1245.

PMID: 38236461 DOI: 10.1007/s12033-023-01025-1.

Prediction of diagnostic gene biomarkers for hypertrophic cardiomyopathy by integrated machine learning.

You H, Dong M J Int Med Res. 2023; 51(11):3000605231213781.

PMID: 38006610 PMC: 10683566. DOI: 10.1177/03000605231213781.

Identification of crucial genes related to heart failure based on GEO database.

Chen Y, Xue J, Yan X, Fang D, Li F, Tian X BMC Cardiovasc Disord. 2023; 23(1):376.

PMID: 37507655 PMC: 10385922. DOI: 10.1186/s12872-023-03400-x.

Multiple-model machine learning identifies potential functional genes in dilated cardiomyopathy.

Zhang L, Lin Y, Wang K, Han L, Zhang X, Gao X Front Cardiovasc Med. 2023; 9:1044443.

PMID: 36712235 PMC: 9874116. DOI: 10.3389/fcvm.2022.1044443.

References

Munthe-Fog L, Hummelshoj T, Ma Y, Hansen B, Koch C, Madsen H . Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state. Mol Immunol. 2008; 45(9):2660-6. DOI: 10.1016/j.molimm.2007.12.012. View

Kim H, Cho E, Yoo J, Kim P, Shin J, Kim M . Proteome analysis of serum from type 2 diabetics with nephropathy. J Proteome Res. 2007; 6(2):735-43. DOI: 10.1021/pr060489g. View

Oliveira G, Brann C, Becker K, Thohan V, Koerner M, Loebe M . Dynamic expression of the membrane attack complex (MAC) of the complement system in failing human myocardium. Am J Cardiol. 2006; 97(11):1626-9. DOI: 10.1016/j.amjcard.2005.12.056. View

Zimmermann O, Kochs M, Zwaka T, Bienek-Ziolkowski M, Hoher M, Hombach V . Prognostic role of myocardial tumor necrosis factor-alpha and terminal complement complex expression in patients with dilated cardiomyopathy. Eur J Heart Fail. 2006; 9(1):51-4. DOI: 10.1016/j.ejheart.2006.04.001. View

Wang C, Yim K, Poon T, Choy K, Chu C, Lui W . Innate immune response by ficolin binding in apoptotic placenta is associated with the clinical syndrome of preeclampsia. Clin Chem. 2007; 53(1):42-52. DOI: 10.1373/clinchem.2007.074401. View

McMurray J, Adamopoulos S, Anker S, Auricchio A, Bohm M, Dickstein K . ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the.... Eur J Heart Fail. 2012; 14(8):803-69. DOI: 10.1093/eurjhf/hfs105. View

Clark D, Cleman M, Pfau S, Rollins S, Ramahi T, Mayer C . Serum complement activation in congestive heart failure. Am Heart J. 2001; 141(4):684-90. DOI: 10.1067/mhj.2001.113758. View

Munthe-Fog L, Hummelshoj T, Hansen B, Koch C, Madsen H, Skjodt K . The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels. Scand J Immunol. 2007; 65(4):383-92. DOI: 10.1111/j.1365-3083.2007.01915.x. View

Bay J, Hein E, Sorensen S, Hansen J, Garred P . Pre-transplant levels of ficolin-3 are associated with kidney graft survival. Clin Immunol. 2013; 146(3):240-7. DOI: 10.1016/j.clim.2013.01.005. View

10.

Walport M . Complement. First of two parts. N Engl J Med. 2001; 344(14):1058-66. DOI: 10.1056/NEJM200104053441406. View

11.

Li R, Chen H, Tu K, Zhao S, Zhou H, Li S . Localized-statistical quantification of human serum proteome associated with type 2 diabetes. PLoS One. 2008; 3(9):e3224. PMC: 2529402. DOI: 10.1371/journal.pone.0003224. View

12.

Kaslow R, Carrington M, Apple R, Park L, Munoz A, Saah A . Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med. 1996; 2(4):405-11. DOI: 10.1038/nm0496-405. View

13.

Garred P, Madsen H, Kurtzhals J, Lamm L, Thiel S, Hey A . Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans. Eur J Immunogenet. 1992; 19(6):403-12. DOI: 10.1111/j.1744-313x.1992.tb00083.x. View

14.

Whelan R, Kaplinskiy V, Kitsis R . Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol. 2010; 72:19-44. DOI: 10.1146/annurev.physiol.010908.163111. View

15.

Gombos T, Forhecz Z, Pozsonyi Z, Szeplaki G, Kunde J, Fust G . Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure. Clin Res Cardiol. 2012; 101(8):607-15. DOI: 10.1007/s00392-012-0432-6. View

16.

Honore C, Rorvig S, Munthe-Fog L, Hummelshoj T, Madsen H, Borregaard N . The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma. Mol Immunol. 2008; 45(10):2782-9. DOI: 10.1016/j.molimm.2008.02.005. View

17.

Hummelshoj T, Fog L, Madsen H, Sim R, Garred P . Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen). Mol Immunol. 2007; 45(6):1623-32. DOI: 10.1016/j.molimm.2007.10.006. View

18.

Jensen M, Honore C, Hummelshoj T, Hansen B, Madsen H, Garred P . Ficolin-2 recognizes DNA and participates in the clearance of dying host cells. Mol Immunol. 2006; 44(5):856-65. DOI: 10.1016/j.molimm.2006.04.002. View

19.

Wrigley B, Lip G, Shantsila E . The role of monocytes and inflammation in the pathophysiology of heart failure. Eur J Heart Fail. 2011; 13(11):1161-71. DOI: 10.1093/eurjhf/hfr122. View

20.

Ma Y, Skjoedt M, Garred P . Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex. J Innate Immun. 2012; 5(3):242-50. PMC: 6741501. DOI: 10.1159/000345356. View