Počet záznamů: 1
Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin
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SYSNO ASEP 0536862 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin Tvůrce(i) Janovská, Petra (FGU-C) RID, ORCID
Melenovský, V. (CZ)
Svobodová, Michaela (FGU-C) RID, ORCID
Havlenová, T. (CZ)
Kratochvílová, H. (CZ)
Haluzík, M. (CZ)
Hošková, E. (CZ)
Pelikánová, T. (CZ)
Kautzner, J. (CZ)
Monzo, L. (CZ)
Jurcová, I. (CZ)
Adamcová, Kateřina (FGU-C) ORCID, RID
Leňková, Lucie (FGU-C) ORCID, RID
Burešová, Jana (FGU-C) ORCID, RID
Rossmeisl, Martin (FGU-C) RID, ORCID
Kuda, Ondřej (FGU-C) RID, ORCID, SAI
Čajka, Tomáš (FGU-C) RID, ORCID, SAI
Kopecký, Jan (FGU-C) RID, ORCIDZdroj.dok. Journal of Cachexia Sarcopenia and Muscle. - : Wiley - ISSN 2190-5991
Roč. 11, č. 6 (2020), s. 1614-1627Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova heart failure ; lipolysis ; natriuretic peptides ; adipose tissue ; cardiolipin ; cardiac cachexia Vědní obor RIV FA - Kardiovaskulární nemoci vč. kardiochirurgie Obor OECD Cardiac and Cardiovascular systems CEP NV17-28784A GA MZd - Ministerstvo zdravotnictví NV16-27496A GA MZd - Ministerstvo zdravotnictví NV19-02-00118 GA MZd - Ministerstvo zdravotnictví Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000579656200001 EID SCOPUS 85092778345 DOI 10.1002/jcsm.12631 Anotace Background Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods The study was conducted in advanced HF patients (n = 52, 83% male patients) undergoing heart transplantation. Patients with >= 7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP, 2007 +/- 1229 vs. 1411 +/- 1272 pg/mL,P = 0.010) and lower EAT thickness (2.1 +/- 0.8 vs. 2.9 +/- 1.4 mm,P = 0.010), and they were treated with similar to 2.5-fold lower dose of both beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis, variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = -0.94,P = 0.036). Conclusions Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and 'healthy' EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and beta-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2021 Elektronická adresa https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12631
Počet záznamů: 1