Skip to main content

Advertisement

SpringerLink
Log in

Characterization of Plasma SDS-Protein Aggregation Profile of Patients with Heart Failure with Preserved Ejection Fraction

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

This study characterizes the plasma levels and composition of SDS-resistant aggregates (SRAs) in patients with heart failure with preserved ejection fraction (HFpEF) to infer molecular pathways associated with disease and/or proteostasis disruption. Twenty adults (ten with HFpEF and ten age-matched individuals) were included. Circulating SRAs were resolved by diagonal two-dimensional SDS-PAGE, and their protein content was identified by mass spectrometry. Protein carbonylation, ubiquitination and ficolin-3 were evaluated. Patients with HFpEF showed higher SRA/total (36.6 ± 4.9% vs 29.6 ± 2.2%, p = 0.009) and SRA/soluble levels (58.6 ± 12.7% vs 40.6 ± 5.8%, p = 0.008). SRAs were carbonylated and ubiquitinated, suggesting they are composed of dysfunctional proteins resistant to degradation. SRAs were enriched in proteins associated with cardiovascular function/disease and with proteostasis machinery. Total ficolin-3 levels were decreased (0.77 ± 0.22, p = 0.041) in HFpEF, suggesting a reduced proteostasis capacity to clear circulating SRA. Thus, the higher accumulation of SRA in HFpEF may result from a failure or overload of the protein clearance machinery.

Graphical abstract

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contributio. Eur Heart J. 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368.

    Article  CAS  PubMed  Google Scholar 

  2. van Heerebeek L, Paulus WJ. Understanding heart failure with preserved ejection fraction: where are we today? Netherlands Hear J. 2016;24:227–36. https://doi.org/10.1007/s12471-016-0810-1.

    Article  Google Scholar 

  3. Nanayakkara S, Kaye DM. Management of heart failure with preserved ejection fraction: a review. Clin Ther. 2015;37:2186–98. https://doi.org/10.1016/j.clinthera.2015.08.005.

    Article  PubMed  Google Scholar 

  4. Santos M, Opotowsky AR, Shah AM, Tracy J, Waxman AB, Systrom DM. Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction. Circ Hear Fail. 2015;8:278–85. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001551.

    Article  Google Scholar 

  5. Mishra S, Kass DA. Cellular and molecular pathobiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2021;18:400–23. https://doi.org/10.1038/s41569-020-00480-6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ayyadevara S, Mercanti F, Wang X, Mackintosh SG, Tackett AJ, Prayaga SVS, Romeo F, Shmookler Reis RJ, Mehta JL. Age- and hypertension-associated protein aggregates in mouse heart have similar proteomic profiles. Hypertension. 2016;67:1006–13. https://doi.org/10.1161/HYPERTENSIONAHA.115.06849.

    Article  CAS  PubMed  Google Scholar 

  7. Evangelisti A, Butler H, Del Monte F. The heart of the Alzheimer’s: a mindful view of heart disease. Front Physiol. 2020;11:625974. https://doi.org/10.3389/fphys.2020.625974.

    Article  PubMed  Google Scholar 

  8. González-López E, Gallego-Delgado M, Guzzo-Merello G, de Haro-del Moral FJ, Cobo-Marcos M, Robles C, Bornstein B, Salas C, Lara-Pezzi E, Alonso-Pulpon L, Garcia-Pavia P. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36:2585–94. https://doi.org/10.1093/eurheartj/ehv338.

    Article  CAS  PubMed  Google Scholar 

  9. Hahn VS, Yanek LR, Vaishnav J, Ying W, Vaidya D, Lee YZJ, Riley SJ, Subramanya V, Brown EE, Hopkins CD, Ononogbu S, Perzel Mandell K, Halushka MK, Steenbergen C, Rosenberg AZ, Tedford RJ, Judge DP, Shah SJ, Russell SD, Kass DA, Sharma K. Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis. JACC Hear Fail. 2020;8:712–24. https://doi.org/10.1016/j.jchf.2020.04.007.

    Article  Google Scholar 

  10. Henning RH, Brundel BJJM. Proteostasis in cardiac health and disease. Nat Rev Cardiol. 2017;14:637–653. https://doi.org/10.1038/nrcardio.2017.89.

  11. Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol. 2019;20:421–35. https://doi.org/10.1038/s41580-019-0101-y.

    Article  CAS  PubMed  Google Scholar 

  12. Hofmann C, Katus HA, Doroudgar S. Protein misfolding in cardiac disease. Circulation. 2019;139:2085–8. https://doi.org/10.1161/CIRCULATIONAHA.118.037417.

    Article  PubMed  Google Scholar 

  13. Wiersma M, Henning RH, Brundel BJJM. Derailed proteostasis as a determinant of cardiac aging. Can J Cardiol. 2016;32:1166.e11-1166.e20. https://doi.org/10.1016/j.cjca.2016.03.005.

    Article  PubMed  Google Scholar 

  14. Willis MS, Patterson C. Proteotoxicity and cardiac dysfunction — Alzheimer’s disease of the heart? N Engl J Med. 2013;368:455–64. https://doi.org/10.1056/NEJMra1106180.

    Article  CAS  PubMed  Google Scholar 

  15. Klaips CL, Jayaraj GG, Hartl FU. Pathways of cellular proteostasis in aging and disease. J Cell Biol. 2017;217:51–63. https://doi.org/10.1083/jcb.201709072.

    Article  CAS  PubMed  Google Scholar 

  16. Morimoto RI. Cell-nonautonomous regulation of proteostasis in aging and disease. Cold Spring Harb Perspect Biol. 2020;12:a034074. https://doi.org/10.1101/cshperspect.a034074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sala AJ, Bott LC, Morimoto RI. Shaping proteostasis at the cellular, tissue, and organismal level. J Cell Biol. 2017;216:1231–41. https://doi.org/10.1083/jcb.201612111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Labbadia J, Morimoto RI. The biology of proteostasis in aging and disease. Annu Rev Biochem. 2015;84:435–64. https://doi.org/10.1146/annurev-biochem-060614-033955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Islam M, Diwan A, Mani K. Come together: protein assemblies, aggregates and the sarcostat at the heart of cardiac myocyte homeostasis. Front Physiol. 2020;11:586. https://doi.org/10.3389/fphys.2020.00586.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Felker GM, Mann DL (2019) Heart failure: a companion to Braunwald’s heart disease e-book. Elsevier Health Sciences

  21. Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med. 2007;13:619–24. https://doi.org/10.1038/nm1574.

    Article  CAS  PubMed  Google Scholar 

  22. Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, Le V, Levine B, Rothermel BA, Hill JA. Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest. 2007;117:1782–93. https://doi.org/10.1172/JCI27523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Day SM, Divald A, Wang P, Davis F, Bartolone S, Jones R, Powell SR. Impaired assembly and post-translational regulation of 26S proteasome in human end-stage heart failure. Circ Hear Fail. 2013;6:544–9. https://doi.org/10.1161/CIRCHEARTFAILURE.112.000119.

    Article  CAS  Google Scholar 

  24. Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM. Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies. Circulation. 2010;121:997–1004. https://doi.org/10.1161/CIRCULATIONAHA.109.904557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schiattarella GG, Altamirano F, Tong D, French KM, Villalobos E, Kim SY, Luo X, Jiang N, May HI, Wang ZV, Hill TM, Mammen PPA, Huang J, Lee DI, Hahn VS, Sharma K, Kass DA, Lavandero S, Gillette TG, Hill JA. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019;568:351–6. https://doi.org/10.1038/s41586-019-1100-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Uversky VN. Mysterious oligomerization of the amyloidogenic proteins. FEBS J. 2010;277:2940–53. https://doi.org/10.1111/j.1742-4658.2010.07721.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gorza L, del Monte F. Protein unfolding in cardiomyopathies. Heart Fail Clin. 2005;1:237–50. https://doi.org/10.1016/j.hfc.2005.03.009.

    Article  PubMed  Google Scholar 

  28. Gouveia M, Xia K, Colón W, Vieira SI, Ribeiro F. Protein aggregation, cardiovascular diseases, and exercise training: where do we stand? Ageing Res Rev. 2017;40:1–10. https://doi.org/10.1016/j.arr.2017.07.005.

    Article  CAS  PubMed  Google Scholar 

  29. Pattison JS, Sanbe A, Maloyan A, Osinska H, Klevitsky R, Robbins J. Cardiomyocyte expression of a polyglutamine preamyloid oligomer causes heart failure. Circulation. 2008;117:2743–51. https://doi.org/10.1161/CIRCULATIONAHA.107.750232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rubin J, Maurer MS. Cardiac amyloidosis: overlooked, underappreciated, and treatable. Annu Rev Med. 2020;71:203–19. https://doi.org/10.1146/annurev-med-052918-020140.

    Article  CAS  PubMed  Google Scholar 

  31. Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A, Robbins J. Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A. 2004;101:10132–6. https://doi.org/10.1073/pnas.0401900101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Diteepeng T, del Monte F, Luciani M. The long and winding road to target protein misfolding in cardiovascular diseases. Eur J Clin Invest. 2021;51: e13504. https://doi.org/10.1111/eci.13504.

    Article  CAS  PubMed  Google Scholar 

  33. Millen KR, Buhimschi CS, Zhao G, Rood KM, Tabbah S, Buhimschi IA. Serum and urine thioflavin-T–enhanced fluorescence in severe preeclampsia. Hypertension. 2018;71:1185–92. https://doi.org/10.1161/HYPERTENSIONAHA.118.11034.

    Article  CAS  PubMed  Google Scholar 

  34. Xia K, Trasatti H, Wymer JP, Colón W. Increased levels of hyper-stable protein aggregates in plasma of older adults. Age. 2016;38:1–9. https://doi.org/10.1007/s11357-016-9919-9.

    Article  CAS  Google Scholar 

  35. Adiutori R, Puentes F, Bremang M, Lombardi V, Zubiri I, Leoni E, Aarum J, Sheer D, McArthur S, Pike I, Malaspina A (2021) Analysis of circulating protein aggregates as a route of investigation into neurodegenerative disorders. Brain Commun 3:fcab148. https://doi.org/10.1093/braincomms/fcab148

  36. Manning M, Colón W. Structural basis of protein kinetic stability: resistance to sodium dodecyl sulfate suggests a central role for rigidity and a bias toward β-sheet structure. Biochemistry. 2004;43:11248–54. https://doi.org/10.1021/bi0491898.

    Article  CAS  PubMed  Google Scholar 

  37. Wyatt AR, Yerbury JJ, Poon S, Wilson MR. Therapeutic targets in extracellular protein deposition diseases. Curr Med Chem. 2009;16:2855–66. https://doi.org/10.2174/092986709788803187.

    Article  CAS  PubMed  Google Scholar 

  38. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola V-P, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Group ESCSD. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of. Eur Heart J. 2016;37:2129–200. https://doi.org/10.1093/eurheartj/ehw128.

    Article  PubMed  Google Scholar 

  39. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I. 2018 ESC/ESH guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39:3021–104. https://doi.org/10.1093/eurheartj/ehy339.

    Article  PubMed  Google Scholar 

  40. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt J-U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1-39.e14. https://doi.org/10.1016/j.echo.2014.10.003.

    Article  PubMed  Google Scholar 

  41. Committee ATS, on Proficiency Standards for Clinical Pulmonary Function Laboratories,. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111–7. https://doi.org/10.1164/ajrccm.166.1.at1102.

    Article  Google Scholar 

  42. Deutsch EW, Bandeira N, Sharma V, Perez-Riverol Y, Carver JJ, Kundu DJ, García-Seisdedos D, Jarnuczak AF, Hewapathirana S, Pullman BS, Wertz J, Sun Z, Kawano S, Okuda S, Watanabe Y, Hermjakob H, MacLean B, MacCoss MJ, Zhu Y, Ishihama Y, Vizcaíno JA. The ProteomeXchange consortium in 2020: enabling ‘big data’ approaches in proteomics. Nucleic Acids Res. 2020;48:D1145–52. https://doi.org/10.1093/nar/gkz984.

    Article  CAS  PubMed  Google Scholar 

  43. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, von Mering C. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–13. https://doi.org/10.1093/nar/gky1131.

    Article  CAS  PubMed  Google Scholar 

  44. Chiti F, Stefani M, Taddei N, Ramponi G, Dobson CM. Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature. 2003;424:805–8. https://doi.org/10.1038/nature01891.

    Article  CAS  PubMed  Google Scholar 

  45. Knowles TPJ, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol. 2014;15:384–396. https://doi.org/10.1038/nrm3810.

  46. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982;157:105–32. https://doi.org/10.1016/0022-2836(82)90515-0.

    Article  CAS  PubMed  Google Scholar 

  47. Basisty N, Schilling B, Rabinovitch PS. Identifying ubiquitinated proteins and aggregates. Aging (Albany NY). 2018;10:2549–50. https://doi.org/10.18632/aging.101605.

    Article  PubMed  Google Scholar 

  48. Kostin S, Pool L, Elsässer A, Hein S, Drexler HCA, Arnon E, Hayakawa Y, Zimmermann R, Bauer E, Klövekorn W-P, Schaper J. Myocytes die by multiple mechanisms in failing human hearts. Circ Res. 2003;92:715–24. https://doi.org/10.1161/01.RES.0000067471.95890.5C.

    Article  CAS  PubMed  Google Scholar 

  49. Tanase M, Urbanska AM, Zolla V, Clement CC, Huang L, Morozova K, Follo C, Goldberg M, Roda B, Reschiglian P, Santambrogio L. Role of carbonyl modifications on aging-associated protein aggregation. Sci Rep. 2016;6:19311. https://doi.org/10.1038/srep19311.

  50. Cater JH, Kumita JR, Abdallah RZ, Zhao G, Bernardo-Gancedo A, Henry A, Winata W, Chi M, Grenyer BSF, Townsend ML, Ranson M, Buhimschi CS, Charnock-Jones DS, Dobson CM, Wilson MR, Buhimschi IA, Wyatt AR. Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer’s-associated amyloid beta peptide. Proc Natl Acad Sci. 2019;116:6101–10. https://doi.org/10.1073/pnas.1817298116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Finn TE, Nunez AC, Sunde M, Easterbrook-Smith SB. Serum albumin prevents protein aggregation and amyloid formation and retains chaperone-like activity in the presence of physiological ligands. J Biol Chem. 2012;287:21530–40. https://doi.org/10.1074/jbc.M112.372961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tang H, Fu Y, Cui Y, He Y, Zeng X, Ploplis VA, Castellino FJ, Luo Y. Fibrinogen has chaperone-like activity. Biochem Biophys Res Commun. 2009;378:662–7. https://doi.org/10.1016/j.bbrc.2008.11.112.

    Article  CAS  PubMed  Google Scholar 

  53. Wyatt AR, Wilson MR. Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma. Cell Stress Chaperones. 2013;18:161–70. https://doi.org/10.1007/s12192-012-0365-z.

    Article  CAS  PubMed  Google Scholar 

  54. Wyatt AR, Yerbury JJ, Ecroyd H, Wilson MR. Extracellular chaperones and proteostasis. Annu Rev Biochem. 2013;82:295–322. https://doi.org/10.1146/annurev-biochem-072711-163904.

    Article  CAS  PubMed  Google Scholar 

  55. Buhimschi IA, Nayeri UA, Zhao G, Shook LL, Pensalfini A, Funai EF, Bernstein IM, Glabe CG, Buhimschi CS (2014) Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia. Sci Transl Med 6:245ra92. https://doi.org/10.1126/scitranslmed.3008808

  56. Gillmore JD, Lachmann HJ, Rowczenio D, Gilbertson JA, Zeng C-H, Liu Z-H, Li L-S, Wechalekar A, Hawkins PN. Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen Aα-chain amyloidosis. J Am Soc Nephrol. 2009;20:444–51. https://doi.org/10.1681/ASN.2008060614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kim JW, Byun MS, Lee JH, Yi D, Jeon SY, Sohn BK, Lee J-Y, Shin SA, Kim YK, Kang KM, Sohn C-H, Lee DY, Group for the KR. Serum albumin and beta-amyloid deposition in the human brain. Neurology. 2020;95:e815–26. https://doi.org/10.1212/WNL.0000000000010005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sergeeva VA, Zakharova NV, Bugrova AE, Starodubtseva NL, Indeykina MI, Kononikhin AS, Frankevich VE, Nikolaev EN. The high-resolution mass spectrometry study of the protein composition of amyloid-like urine aggregates associated with preeclampsia. Eur J Mass Spectrom. 2019;26:158–61. https://doi.org/10.1177/1469066719860076.

    Article  CAS  Google Scholar 

  59. Varma VR, Varma S, An Y, Hohman TJ, Seddighi S, Casanova R, Beri A, Dammer EB, Seyfried NT, Pletnikova O, Moghekar A, Wilson MR, Lah JJ, O’Brien RJ, Levey AI, Troncoso JC, Albert MS, Thambisetty M. Alpha-2 macroglobulin in Alzheimer’s disease: a marker of neuronal injury through the RCAN1 pathway. Mol Psychiatry. 2017;22:13–23. https://doi.org/10.1038/mp.2016.206.

    Article  CAS  PubMed  Google Scholar 

  60. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Haptoglobin and risk of myocardial infarction, stroke, and congestive heart failure in 342,125 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Ann Med. 2009;41:522–32. https://doi.org/10.1080/07853890903089453.

    Article  CAS  PubMed  Google Scholar 

  61. Lu D-Y, Lin C-P, Wu C-H, Cheng T-M, Pan J-P. Plasma haptoglobin level can augment NT-proBNP to predict poor outcome in patients with severe acute decompensated heart failure. J Investig Med. 2019;67:20–7. https://doi.org/10.1136/jim-2018-000710.

    Article  PubMed  Google Scholar 

  62. Prohászka Z, Munthe-Fog L, Ueland T, Gombos T, Yndestad A, Förhécz Z, Skjoedt M-O, Pozsonyi Z, Gustavsen A, Jánoskuti L, Karádi I, Gullestad L, Dahl CP, Askevold ET, Füst G, Aukrust P, Mollnes TE, Garred P. Association of ficolin-3 with severity and outcome of chronic heart failure. PLoS ONE. 2013;8:e60976. https://doi.org/10.1371/journal.pone.0060976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dogan A. Amyloidosis: insights from proteomics. Annu Rev Pathol Mech Dis. 2017;12:277–304. https://doi.org/10.1146/annurev-pathol-052016-100200.

    Article  CAS  Google Scholar 

  64. Kaushik S, Cuervo AM. Proteostasis and aging. Nat Med. 2015;21:1406–15. https://doi.org/10.1038/nm.4001.

    Article  CAS  PubMed  Google Scholar 

  65. Dubrey SW, Hawkins PN, Falk RH. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart. 2011;97:75–84. https://doi.org/10.1136/hrt.2009.190405.

    Article  CAS  PubMed  Google Scholar 

  66. Vergaro G, Aimo A, Barison A, Genovesi D, Buda G, Passino C, Emdin M. Keys to early diagnosis of cardiac amyloidosis: red flags from clinical, laboratory and imaging findings. Eur J Prev Cardiol. 2020;27:1806–15. https://doi.org/10.1177/2047487319877708.

    Article  PubMed  Google Scholar 

  67. Fine NM. Challenges and strategies in the diagnosis of cardiac amyloidosis. Can J Cardiol. 2020;36:441–3. https://doi.org/10.1016/j.cjca.2019.09.017.

    Article  PubMed  Google Scholar 

  68. Nevone A, Merlini G, Nuvolone M. Treating protein misfolding diseases: therapeutic successes against systemic amyloidoses. Front Pharmacol. 2020;11:1024. https://doi.org/10.3389/fphar.2020.01024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Xia K, Zhang S, Bathrick B, Liu S, Garcia Y, Colón W. Quantifying the kinetic stability of hyperstable proteins via time-dependent SDS trapping. Biochemistry. 2012;51:100–7. https://doi.org/10.1021/bi201362z.

    Article  CAS  PubMed  Google Scholar 

  70. Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A. Protein carbonylation in human diseases. Trends Mol Med. 2003;9:169–76. https://doi.org/10.1016/S1471-4914(03)00031-5.

    Article  CAS  PubMed  Google Scholar 

  71. Fan R, Schrott LM, Snelling S, Felty J, Graham D, McGauly PL, Arnold T, Korneeva NL. Carbonyl-protein content increases in brain and blood of female rats after chronic oxycodone treatment. BMC Neurosci. 2020;21:4. https://doi.org/10.1186/s12868-020-0552-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Basisty NB, Liu Y, Reynolds J, Karunadharma PP, Dai D-F, Fredrickson J, Beyer RP, MacCoss MJ, Rabinovitch PS. Stable isotope labeling reveals novel insights into ubiquitin-mediated protein aggregation with age, calorie restriction, and rapamycin treatment. J Gerontol Ser A. 2018;73:561–70. https://doi.org/10.1093/gerona/glx047.

    Article  CAS  Google Scholar 

  73. Weekes J, Morrison K, Mullen A, Wait R, Barton P, Dunn MJ. Hyperubiquitination of proteins in dilated cardiomyopathy. Proteomics. 2003;3:208–16. https://doi.org/10.1002/pmic.200390029.

    Article  CAS  PubMed  Google Scholar 

  74. Walther DM, Kasturi P, Zheng M, Pinkert S, Vecchi G, Ciryam P, Morimoto RI, Dobson CM, Vendruscolo M, Mann M, Hartl FU. Widespread proteome remodeling and aggregation in aging C. elegans. Cell. 2015;161:919–32. https://doi.org/10.1016/j.cell.2015.03.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Eulitz M, Weiss DT, Solomon A. Immunoglobulin heavy-chain-associated amyloidosis. Proc Natl Acad Sci. 1990;87:6542–6. https://doi.org/10.1073/pnas.87.17.6542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Glenner GG, Terry W, Harada M, Isersky C, Page D. Amyloid fibril proteins proof of homology with immunoglobulin light chains by sequence analyses. Science (80). 1971;172:1150–1. https://doi.org/10.1126/science.172.3988.1150.

    Article  CAS  Google Scholar 

  77. Glenner GG, Harbaugh J, Ohms JI, Harada M, Cuatrecasas P. An amyloid protein: the amino-terminal variable fragment of an immunoglobulin light chain. Biochem Biophys Res Commun. 1970;41:1287–9. https://doi.org/10.1016/0006-291X(70)90227-5.

    Article  CAS  PubMed  Google Scholar 

  78. Hasib Sidiqi M, Gertz MA. Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021. Blood Cancer J. 2021;11:90. https://doi.org/10.1038/s41408-021-00483-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hammadah M, Fan Y, Wu Y, Hazen SL, Tang WHW. Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure. J Card Fail. 2014;20:946–52. https://doi.org/10.1016/j.cardfail.2014.08.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Suzuki S, Hashizume N, Kanzaki Y, Maruyama T, Kozuka A, Yahikozawa K. Prognostic significance of serum albumin in patients with stable coronary artery disease treated by percutaneous coronary intervention. PLoS ONE. 2019;14:e0219044. https://doi.org/10.1371/journal.pone.0219044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Dabbs RA, Wyatt AR, Yerbury JJ, Ecroyd H, Wilson MR. Extracellular chaperones. Top Curr Chem. 2013;328:241–68. https://doi.org/10.1007/128_2011_262.

    Article  CAS  PubMed  Google Scholar 

  82. Wilson MR, Yerbury JJ, Poon S. Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol Biosyst. 2008;4:42–52. https://doi.org/10.1039/B712728F.

    Article  CAS  PubMed  Google Scholar 

  83. Mannini B, Chiti F. Chaperones as suppressors of protein misfolded oligomer toxicity. Front Mol Neurosci. 2017;10:98. https://doi.org/10.3389/fnmol.2017.00098.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yerbury JJ, Ooi L, Dillin A, Saunders DN, Hatters DM, Beart PM, Cashman NR, Wilson MR, Ecroyd H. Walking the tightrope: proteostasis and neurodegenerative disease. J Neurochem. 2016;137:489–505. https://doi.org/10.1111/jnc.13575.

    Article  CAS  PubMed  Google Scholar 

  85. Langlois MR, Delanghe JR. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem. 1996;42:1589–600. https://doi.org/10.1093/clinchem/42.10.1589.

    Article  CAS  PubMed  Google Scholar 

  86. di Masi A, De Simone G, Ciaccio C, D’Orso S, Coletta M, Ascenzi P. Haptoglobin: From hemoglobin scavenging to human health. Mol Aspects Med. 2020;73:100851. https://doi.org/10.1016/j.mam.2020.100851.

    Article  CAS  PubMed  Google Scholar 

  87. Spagnuolo MS, Maresca B, La Marca V, Carrizzo A, Veronesi C, Cupidi C, Piccoli T, Maletta RG, Bruni AC, Abrescia P, Cigliano L. Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their crosstalk. ACS Chem Neurosci. 2014;5:837–47. https://doi.org/10.1021/cn500099f.

    Article  CAS  PubMed  Google Scholar 

  88. Haas B, Serchi T, Wagner DR, Gilson G, Planchon S, Renaut J, Hoffmann L, Bohn T, Devaux Y. Proteomic analysis of plasma samples from patients with acute myocardial infarction identifies haptoglobin as a potential prognostic biomarker. J Proteomics. 2011;75:229–36. https://doi.org/10.1016/j.jprot.2011.06.028.

    Article  CAS  PubMed  Google Scholar 

  89. Yerbury JJ, Rybchyn MS, Easterbrook-Smith SB, Henriques C, Wilson MR. The acute phase protein haptoglobin is a mammalian extracellular chaperone with an action similar to clusterin. Biochemistry. 2005;44:10914–25. https://doi.org/10.1021/bi050764x.

    Article  CAS  PubMed  Google Scholar 

  90. Hummelshoj T, Fog LM, Madsen HO, Sim RB, Garred P. Comparative study of the human ficolins reveals unique features of ficolin-3 (Hakata antigen). Mol Immunol. 2008;45:1623–32. https://doi.org/10.1016/j.molimm.2007.10.006.

    Article  CAS  PubMed  Google Scholar 

  91. Endo Y, Matsushita M, Fujita T. New insights into the role of ficolins in the lectin pathway of innate immunity. Int Rev Cell Mol Biol. 2015;316:49–110. https://doi.org/10.1016/bs.ircmb.2015.01.003.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Portuguese Foundation for Science and Technology [PTDC/MEC- CAR/30011/2017], financed by FCT and co-financed by the FEDER under the new Partnership Agreement PT2020 within the project POCI- 01-0145-FEDER-030011 and the research units iBiMED (UID/BIM/04501/2020), LAV-REQUIMTE (UIDB/50006/2020), CIAFEL (UIDB/00617/2020), and UMIB (UIDB/00215/2020 and UIDP/00215/2020), financed by national funds through the FCT. MG and MT are supported by the Ph.D. FCT grant SFRH/BD/128893/2017 and 2020.08565.BD, respectively. CS is supported by an individual grant from CAPES [BEX 0554/14-6].

Author information

Authors and Affiliations

  1. Department of Medical Sciences, iBiMED – Institute of Biomedicine, University of Aveiro, Aveiro, Portugal

    Marisol Gouveia, Manuel Teixeira, Rui Vitorino & Sandra Vieira

  2. Surgery and Physiology Department, Faculty of Medicine, University of Porto, Porto, Portugal

    Cristine Schmidt & Rui Vitorino

  3. Faculty of Sport, Research Center in Physical Activity, Health and Leisure, University of Porto, Porto, Portugal

    Cristine Schmidt

  4. Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal

    Cristine Schmidt & Mário Santos

  5. School of Health Sciences, University of Aveiro, Aveiro, Portugal

    Mário Lopes

  6. Mass Spectrometry Centre, LAQV REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal

    Susana S. Aveiro & Pedro Domingues

  7. GreenCoLab - Green Ocean Association, University of Algarve, Faro, Portugal

    Susana S. Aveiro

  8. Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA

    Ke Xia & Wilfredo Colón

  9. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA

    Ke Xia & Wilfredo Colón

  10. QOPNA &, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal

    Rita Ferreira

  11. Serviço de Cardiologia, Hospital Santo António, Centro Hospitalar Universitário Do Porto, Porto, Portugal

    Mário Santos

  12. UMIB, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

    Mário Santos

  13. School of Health Sciences, iBiMED – Institute of BiomedicineUniversity of AveiroAgras Do Crasto - Campus Universitário de Santiago, Building 30, 3810-193, Aveiro, Portugal

    Fernando Ribeiro

Authors
  1. Marisol Gouveia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristine Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manuel Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mário Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susana S. Aveiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pedro Domingues
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ke Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wilfredo Colón
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rui Vitorino
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rita Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mário Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sandra Vieira
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fernando Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Ribeiro.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Associate Editor Jozine ter Maaten oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Mário Santos, Sandra Vieira and Fernando Ribeiro are equally contributing authors

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 812 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gouveia, M., Schmidt, C., Teixeira, M. et al. Characterization of Plasma SDS-Protein Aggregation Profile of Patients with Heart Failure with Preserved Ejection Fraction. J. of Cardiovasc. Trans. Res. 16, 698–714 (2023). https://doi.org/10.1007/s12265-022-10334-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-022-10334-w

Keywords

Search

Navigation