Please use this identifier to cite or link to this item: https://doi.org/10.1002/ehf2.12699
Title: Extracellular vesicle Cystatin C and CD14 are associated with both renal dysfunction and heart failure
Authors: Verbree-Willemsen, Laura
Zhang, Ya-nan 
Ibrahim, Irwani 
Ooi, Shirley BS
Wang, Jiong-Wei 
Mazlan, Muhammad 
Kuan, Win S 
Chan, Siew-Pang 
Peelen, Linda M
Grobbee, Diederick E
Richards, A Mark 
Lam, Carolyn SP 
de Kleijn, Dominique P 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Heart failure
Renal insufficiency
Extracellular vesicles
Cardiorenal syndrome
CD14
Cystatin C
CARDIOVASCULAR EVENTS
RISK
MORTALITY
DISEASE
DIAGNOSIS
PROGNOSIS
Issue Date: 10-Jul-2020
Publisher: WILEY PERIODICALS, INC
Citation: Verbree-Willemsen, Laura, Zhang, Ya-nan, Ibrahim, Irwani, Ooi, Shirley BS, Wang, Jiong-Wei, Mazlan, Muhammad, Kuan, Win S, Chan, Siew-Pang, Peelen, Linda M, Grobbee, Diederick E, Richards, A Mark, Lam, Carolyn SP, de Kleijn, Dominique P (2020-07-10). Extracellular vesicle Cystatin C and CD14 are associated with both renal dysfunction and heart failure. ESC HEART FAILURE 7 (5). ScholarBank@NUS Repository. https://doi.org/10.1002/ehf2.12699
Abstract: © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: Extracellular vesicles (EVs) are small double-membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. Methods and results: Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub-fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co-morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub-fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub-fractions, and with presence of heart failure in the high density lipoprotein sub-fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub-fractions and in plasma, but not with renal dysfunction. Conclusions: We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.
Source Title: ESC HEART FAILURE
URI: https://scholarbank.nus.edu.sg/handle/10635/177361
ISSN: 20555822
DOI: 10.1002/ehf2.12699
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