Leukocyte Extracellular Vesicles Predict Progression of Systolic Dysfunction in Heart Failure with Mildly Reduced Ejection Fraction (LYCHEE) - A Prospective, Multicentre Cohort Study.

EVs Extracellular vesicles HFmrEF Heart failure Risk stratification

Journal

Journal of cardiovascular translational research
ISSN: 1937-5395
Titre abrégé: J Cardiovasc Transl Res
Pays: United States
ID NLM: 101468585

Informations de publication

Date de publication:
24 Sep 2024
Historique:
received: 29 07 2024
accepted: 12 09 2024
medline: 24 9 2024
pubmed: 24 9 2024
entrez: 24 9 2024
Statut: aheadofprint

Résumé

Risk stratification in heart failure with mildly-reduced ejection fraction (HFmrEF) remains challenging. We evaluated the predictive value of advanced glycation end products (AGEs) and plasma concentrations of extracellular vesicles (EVs) for the systolic and diastolic dysfunction progression in HFmrEF patients. Skin AGE accumulation was measured using AGE Reader. Plasma EV concentrations were measured using flow cytometry. Among 74 patients enrolled, 13 (18%) had systolic dysfunction progression and 5 (7%) had diastolic dysfunction progression during 6.5 months follow-up. Leukocyte EVs concentrations were higher in patients with systolic dysfunction progression (p = 0.002) and predicted the progression with 75.0% sensitivity and 58.3% specificity, independent of other clinical variables (OR 4.72, 95% CI 0.99-22.31). Skin AGE levels and concentrations of other EV subtypes were not associated with systolic or diastolic dysfunction progression. Increased leukocyte EVs concentrations are associated with 4.7-fold higher odds of systolic dysfunction progression in HFmrEF patients.

Identifiants

DOI: 10.1007/s12265-024-10561-3 PMID: 39316271
pubmed: 39316271
doi: 10.1007/s12265-024-10561-3
pii: 10.1007/s12265-024-10561-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Warszawski Uniwersytet Medyczny
ID : 1WR/2/M/MB/N/22
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : VIDI 19724

Informations de copyright

© 2024. The Author(s).

Références

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, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726. https://doi.org/10.1093/eurheartj/ehab368 .
doi: 10.1093/eurheartj/ehab368 pubmed: 34447992
Zhang YN, Vernooij F, Ibrahim I, Ooi S, Gijsberts CM, Schoneveld AH, Sen KW, den Ruijter HM, Timmers L, Richards AM, Jong CT, Mazlan I, Wang JW, Lam CS, de Kleijn DP. Extracellular vesicle proteins associated with systemic vascular events correlate with heart failure: an observational study in a dyspnoea cohort. PLoS ONE. 2016;11(1):e0148073. https://doi.org/10.1371/journal.pone.0148073 .
doi: 10.1371/journal.pone.0148073 pubmed: 26820481 pmcid: 4731211
Zgutka K, Tkacz M, Tomasiak P, Tarnowski M. A role for advanced glycation end products in molecular ageing. Int J Mol Sci. 2023;24(12):9881. https://doi.org/10.3390/ijms24129881 .
doi: 10.3390/ijms24129881 pubmed: 37373042 pmcid: 10298716
Zeng C, Li Y, Ma J, Niu L, Tay FR. Clinical/translational aspects of advanced glycation end-products. Trends Endocrinol Metab. 2019;30(12):959–73. https://doi.org/10.1016/j.tem.2019.08.005 .
doi: 10.1016/j.tem.2019.08.005 pubmed: 31597608
Smit AJ, Hartog JW, Voors AA, van Veldhuisen DJ. Advanced glycation endproducts in chronic heart failure. Ann N Y Acad Sci. 2008;1126:225–30. https://doi.org/10.1196/annals.1433.038 .
doi: 10.1196/annals.1433.038 pubmed: 18448821
Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer UD, Besch HR Jr. Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase. Diabetes. 2004;53(2):463–73. https://doi.org/10.2337/diabetes.53.2.463 .
doi: 10.2337/diabetes.53.2.463 pubmed: 14747299
Hartog JW, Voors AA, Bakker SJ, Smit AJ, van Veldhuisen DJ. Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications. Eur J Heart Fail. 2007;9(12):1146–55. https://doi.org/10.1016/j.ejheart.2007.09.009 .
doi: 10.1016/j.ejheart.2007.09.009 pubmed: 18023248
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28. https://doi.org/10.1038/nrm.2017.125 .
doi: 10.1038/nrm.2017.125 pubmed: 29339798
Gasecka A, Nieuwland R, Budnik M, Dignat-George F, Eyileten C, Harrison P, Huczek Z, Kapłon-Cieślicka A, Lacroix R, Opolski G, Pluta K, van der Pol E, Postuła M, Leroyer A, Siljander P, Sturk A, Filipiak KJ. Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles (AFFECT EV) in acute myocardial infarction. Platelets. 2020;31(1):26–32. https://doi.org/10.1080/09537104.2018.1557616 .
doi: 10.1080/09537104.2018.1557616 pubmed: 30585111
Gąsecka A, Pluta K, Solarska K, Rydz B, Eyileten C, Postula M, van der Pol E, Nieuwland R, Budnik M, Kochanowski J, Jaguszewski MJ, Szarpak Ł, Mazurek T, Kapłon-Cieślicka A, Opolski G, Filipiak KJ. Plasma concentrations of extracellular vesicles are decreased in patients with post-infarct cardiac remodelling. Biology. 2021;10(2):97. https://doi.org/10.3390/biology10020097 .
doi: 10.3390/biology10020097 pubmed: 33573196 pmcid: 7910841
Berezin AE, Kremzer AA, Martovitskaya YV, Berezina TA, Gromenko EA. Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction. EBioMedicine. 2016;4:86–94. https://doi.org/10.1016/j.ebiom.2016.01.018 .
doi: 10.1016/j.ebiom.2016.01.018 pubmed: 26981573 pmcid: 4776070
Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J American Soc Echocardiogr: Off Publ Am Soc Echocardiogr. 2016;29(4):277–314. https://doi.org/10.1016/j.echo.2016.01.011 .
doi: 10.1016/j.echo.2016.01.011
Rolek B, Błażejowska E, Procyk G, Zimodro JM, Gąsecka A. Dedicated devices for non-invasive cardiovascular risk assessment - the future of cardiovascular prevention. Cardiol J. 2024;31(3):496–8. https://doi.org/10.5603/cj.96477 .
doi: 10.5603/cj.96477 pubmed: 38767064 pmcid: 11229805
Coumans FAW, Brisson AR, Buzas EI, Dignat-George F, Drees EEE, El-Andaloussi S, Emanueli C, Gasecka A, Hendrix A, Hill AF, Lacroix R, Lee Y, van Leeuwen TG, Mackman N, Mäger I, Nolan JP, van der Pol E, Pegtel DM, Sahoo S, Siljander PRM, Nieuwland R. Methodological guidelines to study extracellular vesicles. Circ Res. 2017;120(10):1632–48. https://doi.org/10.1161/CIRCRESAHA.117.309417 .
doi: 10.1161/CIRCRESAHA.117.309417 pubmed: 28495994
Welsh JA, Van Der Pol E, Arkesteijn GJA, Bremer M, Brisson A, Coumans F, Dignat-George F, Duggan E, Ghiran I, Giebel B, Görgens A, Hendrix A, Lacroix R, Lannigan J, Libregts SFWM, Lozano-Andrés E, Morales-Kastresana A, Robert S, De Rond L, Tertel T, Jones JC. MIFlowCyt-EV: a framework for standardized reporting of extracellular vesicle flow cytometry experiments. J Extracellular Vesicles. 2020;9(1):1713526. https://doi.org/10.1080/20013078.2020.1713526 .
doi: 10.1080/20013078.2020.1713526
Vilella-Figuerola A, Padró T, Roig E, Mirabet S, Badimon L. New factors in heart failure pathophysiology: Immunity cells release of extracellular vesicles. Front Cardiovasc Med. 2022;9:939625. https://doi.org/10.3389/fcvm.2022.939625 .
doi: 10.3389/fcvm.2022.939625 pubmed: 36407432 pmcid: 9669903
Kain V, Halade GV. Role of neutrophils in ischemic heart failure. Pharmacol Ther. 2020;205:107424. https://doi.org/10.1016/j.pharmthera.2019.107424 .
doi: 10.1016/j.pharmthera.2019.107424 pubmed: 31629005
Altamura M, D’Andrea G, Angelini E, Tortorelli FMP, Balzotti A, Porcelli P, Margaglione M, Brunetti ND, Cassano T, Bellomo A. Psychosomatic syndromes are associated with IL-6 pro-inflammatory cytokine in heart failure patients. PLoS ONE. 2022;17(3):e0265282. https://doi.org/10.1371/journal.pone.0265282 .
doi: 10.1371/journal.pone.0265282 pubmed: 35271674 pmcid: 8912235
Li X, Zeng L, Qu Z, Zhang F. Huoxin pill protects verapamil-induced zebrafish heart failure through inhibition of oxidative stress-triggered inflammation and apoptosis. Heliyon. 2023;10(1):e23402. https://doi.org/10.1016/j.heliyon.2023.e23402 .
doi: 10.1016/j.heliyon.2023.e23402 pubmed: 38169776 pmcid: 10758798
Sarlon-Bartoli G, Bennis Y, Lacroix R, Piercecchi-Marti MD, Bartoli MA, Arnaud L, Mancini J, Boudes A, Sarlon E, Thevenin B, Leroyer AS, Squarcioni C, Magnan PE, Dignat-George F, Sabatier F. Plasmatic level of leukocyte-derived microparticles is associated with unstable plaque in asymptomatic patients with high-grade carotid stenosis. J Am Coll Cardiol. 2013;62(16):1436–41. https://doi.org/10.1016/j.jacc.2013.03.078 .
doi: 10.1016/j.jacc.2013.03.078 pubmed: 23707318
Chironi G, Simon A, Hugel B, Del Pino M, Gariepy J, Freyssinet JM, Tedgui A. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol. 2006;26(12):2775–80. https://doi.org/10.1161/01.ATV.0000249639.36915.04 .
doi: 10.1161/01.ATV.0000249639.36915.04 pubmed: 17038634
Kou Y, Zou L, Liu R, Zhao X, Wang Y, Zhang C, Dong Z, Kou J, Bi Y, Fu L, Shi J. Intravascular cells and circulating microparticles induce procoagulant activity via phosphatidylserine exposure in heart failure. J Thromb Thrombolysis. 2019;48(2):187–94. https://doi.org/10.1007/s11239-019-01889-8 .
doi: 10.1007/s11239-019-01889-8 pubmed: 31177487
Vilella-Figuerola A, Cordero A, Mirabet S, Muñoz-García N, Suades R, Padró T, Badimon L. Platelet-Released Extracellular Vesicle Characteristics Differ in Chronic and in Acute Heart Disease. Thromb Haemost. 2023;123(9):892–903. https://doi.org/10.1055/s-0043-57017 .
doi: 10.1055/s-0043-57017 pubmed: 37075787
Tripisciano C, Weiss R, Eichhorn T, Spittler A, Heuser T, Fischer MB, Weber V. Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin. Sci Rep. 2017;7(1):6522. https://doi.org/10.1038/s41598-017-03262-2 .
doi: 10.1038/s41598-017-03262-2 pubmed: 28747771 pmcid: 5529579
Bettin B, Gasecka A, Li B, Dhondt B, Hendrix A, Nieuwland R, van der Pol E. Removal of platelets from blood plasma to improve the quality of extracellular vesicle research. J Thromb Haemost: JTH. 2022;20(11):2679–85. https://doi.org/10.1111/jth.15867 .
doi: 10.1111/jth.15867 pubmed: 36043239
Arauna D, Chiva-Blanch G, Padró T, Fuentes E, Palomo I, Badimon L. Frail older adults show a distinct plasma microvesicle profile suggesting a prothrombotic and proinflammatory phenotype. J Cell Physiol. 2021;236(3):2099–108. https://doi.org/10.1002/jcp.29996 .
doi: 10.1002/jcp.29996 pubmed: 32749745
De Lorenzo F, Saba N, Kakkar VV. Blood coagulation in patients with chronic heart failure: evidence for hypercoagulable state and potential for pharmacological intervention. Drugs. 2003;63(6):565–76. https://doi.org/10.2165/00003495-200363060-00004 .
doi: 10.2165/00003495-200363060-00004 pubmed: 12656654
Heidland A, Sebeková K, Frangiosa A, De Santo LS, Cirillo M, Rossi F, Cotrufo M, Perna A, Klassen A, Schinzel R, De Santo NG. Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation. Heart (British Cardiac Soc). 2004;90(11):1269–74. https://doi.org/10.1136/hrt.2003.026989 .
doi: 10.1136/hrt.2003.026989
Berg TJ, Snorgaard O, Faber J, Torjesen PA, Hildebrandt P, Mehlsen J, Hanssen KF. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes. Diabetes Care. 1999;22(7):1186–90. https://doi.org/10.2337/diacare.22.7.1186 .
doi: 10.2337/diacare.22.7.1186 pubmed: 10388987
Schäfer S, Huber J, Wihler C, Rütten H, Busch AE, Linz W. Impaired left ventricular relaxation in type 2 diabetic rats is related to myocardial accumulation of N(epsilon)-(carboxymethyl) lysine. Eur J Heart Fail. 2006;8(1):2–6. https://doi.org/10.1016/j.ejheart.2005.04.01134 .
doi: 10.1016/j.ejheart.2005.04.01134 pubmed: 16085456
Hartog JW, Voors AA, Schalkwijk CG, Scheijen J, Smilde TD, Damman K, Bakker SJ, Smit AJ, van Veldhuisen DJ. Clinical and prognostic value of advanced glycation end-products in chronic heart failure. Eur Heart J. 2007;28(23):2879–85. https://doi.org/10.1093/eurheartj/ehm486 .
doi: 10.1093/eurheartj/ehm486 pubmed: 17986469
Lucien F, Gustafson D, Lenassi M, Li B, Teske JJ, Boilard E, von Hohenberg KC, Falcón-Perez JM, Gualerzi A, Reale A, Jones JC, Lässer C, Lawson C, Nazarenko I, O’Driscoll L, Pink R, Siljander PR, Soekmadji C, Hendrix A, Welsh JA, Nieuwland R. MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research. J Extracellular Vesicles. 2023;12(12):e12385. https://doi.org/10.1002/jev2.12385 .
doi: 10.1002/jev2.12385

Auteurs

Aleksandra Gąsecka (A)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.
Laboratory of Experimental Clinical Chemistry & Amsterdam Vesicle Center, Amsterdam UMC, Amsterdam, The Netherlands.

Aleksander Siniarski (A)

Department of Coronary Artery Disease and Heart Failure, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
St. John Paul II Hospital in Krakow, Krakow, Poland.

Piotr Duchnowski (P)

Ambulatory Care Unit, Cardinal Wyszynski National Institute of Cardiology, Warsaw, Poland.

Konrad Stępień (K)

Department of Coronary Artery Disease and Heart Failure, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
St. John Paul II Hospital in Krakow, Krakow, Poland.
Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.

Ewelina Błażejowska (E)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.
Laboratory of Experimental Clinical Chemistry & Amsterdam Vesicle Center, Amsterdam UMC, Amsterdam, The Netherlands.

Magdalena Gajewska (M)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland. gmgajewska@gmail.com.
ORCID: 0000-0003-3373-6236

Kacper Karaban (K)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Kinga Porębska (K)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Aleksandra Reda (A)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Sylwester Rogula (S)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Bartosz Rolek (B)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Dorota Słupik (D)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Roksana Gozdowska (R)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Marcin Kleibert (M)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Dominika Zajkowska (D)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Michał Grąt (M)

Department of General, Gastroenterological and Oncological Surgery, Medical Universityof Warsaw, Warsaw, Poland.

Marcin Grabowski (M)

1St Chair and Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland.

Krzysztof J Filipiak (KJ)

Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
Department of Clinical Sciences, Maria Sklodowska-Curie Medical Academy, Warsaw, Poland.

Edwin van der Pol (E)

Laboratory of Experimental Clinical Chemistry & Amsterdam Vesicle Center, Amsterdam UMC, Amsterdam, The Netherlands.
Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, The Netherlands.

Rienk Nieuwland (R)

Laboratory of Experimental Clinical Chemistry & Amsterdam Vesicle Center, Amsterdam UMC, Amsterdam, The Netherlands.

Classifications MeSH