PDF herunterladen
Horm Metab Res
DOI: 10.1055/a-2563-1187
Original Article: Endocrine Care

Proteomic Profiling of Age-Related Proteins Following Extracorporeal Apheresis

Romy Walther 
1   Department and Outpatient Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany (Ringgold ID: RIN39063)
,
Bhawana Singh 
2   National Heart and Lung Institute, Imperial College London, London, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN4615)
,
Xiaoke Yin
2   National Heart and Lung Institute, Imperial College London, London, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN4615)
,
Philip Mavberg
3   Ayus Medical Group, Basel, Switzerland
,
Anna Mücke
4   INUSpheresis Center Basel, Ayus Medical Group, Basel, Switzerland
,
Roman Rodionov
1   Department and Outpatient Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany (Ringgold ID: RIN39063)
,
Mahmoud Babir
5   Department of Cardiology, Harefield Hospital, Harefield, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN156725)
,
Manuel Mayr
2   National Heart and Lung Institute, Imperial College London, London, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN4615)
,
Stefan R. Bornstein
1   Department and Outpatient Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany (Ringgold ID: RIN39063)
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Lipoprotein apheresis (LA) is often the last option to adequately reduce lipoproteins in patients with familial hypercholesterolemia and lipoprotein (a) hyperlipidemia. Characterized by mild side effects, it is now the most effective method of preventing major cardiovascular events (CVEs). This benefit is due not only to the lowering of lipoprotein levels, but probably also to many other pleiotropic effects that have been extensively described in the literature. These include the reduction of inflammatory signaling substances, fibrinogen, plasminogen or components of the oxidative stress response. Here, we performed a proteomic analysis of 12 patients treated with therapeutic apheresis using two different pore size filters to quantify the effect on age-related plasma proteins. This study showed that important proteins such as α-2-macroglobulin, apolipoprotein C-III, complement C1s subcomponent, C4b-binding protein alpha chain, CD5 antigen-like and pregnancy zone protein, whose role in numerous aging processes has been well described, were significantly reduced by apheresis treatment. We conclude that therapeutic apheresis may be a promising approach to reduce these age-related proteins and that these treatments may become an essential part of managing cardiovascular risk in an aging population.

Keywords

extracorporal apheresis - proteomic analysis - aging


Publikationsverlauf

Eingereicht: 24. Januar 2025

Angenommen nach Revision: 10. März 2025

Artikel online veröffentlicht:
15. April 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Zhao D, Wang Y, Wong ND. et al. Impact of aging on cardiovascular diseases: from chronological observation to biological insights: JACC Fam Ser . JACC Asia 2024; 4: 345-358
    PubMedSuche in Google Scholar
  • 2 Baird GS, Nelson SK, Keeney TR. et al. Age-dependent changes in the cerebrospinal fluid proteome by slow off-rate modified aptamer array. Am J Pathol 2012; 180: 446-456
    PubMedSuche in Google Scholar
  • 3 Ignjatovic V, Lai C, Summerhayes R. et al. Age-related differences in plasma proteins: how plasma proteins change from neonates to adults. PloS One 2011; 6: e17213
    CrossrefPubMedSuche in Google Scholar
  • 4 Moaddel R, Ubaida-Mohien C, Tanaka T. et al. Proteomics in aging research: a roadmap to clinical, translational research. Aging Cell 2021; 20: e13325
    PubMedSuche in Google Scholar
  • 5 Oh HS, Rutledge J, Nachun D. et al. Organ aging signatures in the plasma proteome track health and disease. Nature 2023; 624: 164-172
    PubMedSuche in Google Scholar
  • 6 Rutledge J, Oh H, Wyss-Coray T. Measuring biological age using omics data. Nat Rev Genet 2022; 23: 715-727
    PubMedSuche in Google Scholar
  • 7 Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol 2012; 22: R741-R752
    PubMedSuche in Google Scholar
  • 8 Julius U, Siegert G, Kostka H. et al. Effects of different lipoprotein apheresis methods on serum protein levels. Atheroscler Suppl 2015; 18: 95-102
    CrossrefPubMedSuche in Google Scholar
  • 9 Kopprasch S, Bornstein SR, Bergmann S. et al. Long-term follow-up of circulating oxidative stress markers in patients undergoing lipoprotein apheresis by Direct Adsorption of Lipids (DALI). Atheroscler Suppl 2017; 30: 115-121
    PubMedSuche in Google Scholar
  • 10 Otto C, Geiss HC, Empen K. et al. Long-term reduction of C-reactive protein concentration by regular LDL apheresis. Atherosclerosis 2004; 174: 151-156
    CrossrefPubMedSuche in Google Scholar
  • 11 Tselmin S, Schmitz G, Julius U. et al. Acute effects of lipid apheresis on human serum lipidome. Atheroscler Suppl 2009; 10: 27-33
    PubMedSuche in Google Scholar
  • 12 Yin X, Takov K, Straube R. et al. Precision medicine approach for cardiometabolic risk factors in therapeutic apheresis. Horm Metab Res 2022; 54: 238-249
    Thieme ConnectPubMedSuche in Google Scholar
  • 13 Smyth GK. limma: Linear models for microarray data. In: Gentleman R, Carey VJ, Huber W, Irizarry RA, Dudoit S (eds). Bioinformatics and computational biology solutions using R and bioconductor. New York, NY: Springer; 2005: 397-420
    Suche in Google Scholar
  • 14 [Anonymous] 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis 2019; 290: 140-205
    CrossrefPubMedSuche in Google Scholar
  • 15 Akoumianakis I, Zvintzou E, Kypreos K. et al. ANGPTL3 and apolipoprotein C-III as novel lipid-lowering targets. Curr Atheroscler Rep 2021; 23: 20
    PubMedSuche in Google Scholar
  • 16 Zewinger S, Reiser J, Jankowski V. et al. Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol 2020; 21: 30-41
    PubMedSuche in Google Scholar
  • 17 Jia G, Aroor AR, Jia C. et al. Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 1802-1809
    CrossrefPubMedSuche in Google Scholar
  • 18 Martinelli N, Baroni M, Castagna A. et al. Apolipoprotein C-III strongly correlates with activated factor VII–anti-thrombin complex: an additional link between plasma lipids and coagulation. Thromb Haemost 2019; 119: 192-202
    PubMedSuche in Google Scholar
  • 19 Bergmark BA, Marston NA, Prohaska TA. et al. Olezarsen for hypertriglyceridemia in patients at high cardiovascular risk. N Eng J Med 2024; 390: 1770-1780
    PubMedSuche in Google Scholar
  • 20 Gouni-Berthold I, Schwarz J, Berthold HK. Updates in drug treatment of severe hypertriglyceridemia. Curr Atheroscler Rep 2023; 25: 701-709
    PubMedSuche in Google Scholar
  • 21 Bornfeldt KE. Apolipoprotein C3: form begets function. J Lipid Res 2024; 65: 100475
    PubMedSuche in Google Scholar
  • 22 Marcovina SM, Zoppo A, Viganó-D'Angelo S. et al. Determination of serum levels of complement component C4b-binding protein: influence of age and inflammation. Int J Clin Lab Res 1991; 21: 171-175
    PubMedSuche in Google Scholar
  • 23 Taylor F, Chang A, Ferrell G. et al. C4b-binding protein exacerbates the host response to escherichia coli. Blood 1991; 78: 357-363
    PubMedSuche in Google Scholar
  • 24 Westein E, Denis CV, Bouma BN. et al. The α-chains of C4b-binding protein mediate complex formation with low density lipoprotein receptor-related protein. J Biol Chem 2002; 277: 2511-2516
    PubMedSuche in Google Scholar
  • 25 Dikhoff MJ, ter Weeme M, Vonk AB. et al. C4b-binding protein deposition is induced in diseased aortic heart valves, coinciding with C3d. J Heart Valve Dis 2015; 24: 451-456
    PubMedSuche in Google Scholar
  • 26 Sánchez-Pernaute O, Esparza-Gordillo J, Largo R. et al. Expression of the peptide C4b-binding protein beta in the arthritic joint. Ann Rheum Dis 2006; 65: 1279-1285
    PubMedSuche in Google Scholar
  • 27 Trouw LA, Okroj M, Kupreishvili K. et al. C4b-binding protein is present in affected areas of myocardial infarction during the acute inflammatory phase and covers a larger area than C3. PloS one 2008; 3: e2886
    PubMedSuche in Google Scholar
  • 28 Ma H, Li R, Zhang Z. et al. mRNA level of alpha-2-macroglobulin as an aging biomarker of human fibroblasts in culture. Exp Gerontol 2004; 39: 415-421
    PubMedSuche in Google Scholar
  • 29 Kosmadakis G. Rheopheresis: a narrative review. Int J Artificial Organs 2022; 45: 445-454
    PubMedSuche in Google Scholar
  • 30 Klingel R, Fassbender C, Fassbender T. et al. Rheopheresis: rheologic, functional, and structural aspects. Therap Apheresis 2000; 4: 348-357
    PubMedSuche in Google Scholar
  • 31 Hu Z, Zhang M, Fan J. et al. High-level secretion of pregnancy zone protein is a novel biomarker of DNA damage-induced senescence and promotes spontaneous senescence. J Proteome Res 2023; 22: 3570-3579
    PubMedSuche in Google Scholar
  • 32 Finch S, Shoemark A, Dicker AJ. et al. Pregnancy zone protein is associated with airway infection, neutrophil extracellular trap formation, and disease severity in bronchiectasis. Am J Respir Crit Care Med 2019; 200: 992-1001
    PubMedSuche in Google Scholar
  • 33 Sanjurjo L, Aran G, Roher N. et al. AIM/CD5L: a key protein in the control of immune homeostasis and inflammatory disease. J Leukocyte Biol 2015; 98: 173-184
    PubMedSuche in Google Scholar
  • 34 Castelblanco E, Sarrias MR, Betriu À. et al. Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease. Aging (Albany NY) 2021; 13: 22690-22709
    PubMedSuche in Google Scholar
  • 35 Sinzinger H, Steiner S, Derfler K. Pleiotropic effects of regular lipoprotein-apheresis. Atheroscler Suppl 2017; 30: 122-127
    PubMedSuche in Google Scholar
  • 36 Yuasa Y, Osaki T, Makino H. et al. Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis. Therap Apheresis Dialysis 2014; 18: 93-102
    PubMedSuche in Google Scholar
  • 37 Marlęga-Linert J, Gąsecka A, van der Pol E. et al. Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a). Sci Rep 2024; 14: 2762
    PubMedSuche in Google Scholar