Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00536862" target="_blank" >RIV/67985823:_____/20:00536862 - isvavai.cz</a>

Alternative codes found

RIV/00023001:_____/20:00080457

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12631" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12631</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jcsm.12631" target="_blank" >10.1002/jcsm.12631</a>

Result language

angličtina

Original language name

Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Cachexia Sarcopenia and Muscle

ISSN

2190-5991

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

1614-1627

UT code for WoS article

000579656200001

EID of the result in the Scopus database

2-s2.0-85092778345