Universität zu Köln

Birkenfeld, Andreas L. ORCID: 0000-0003-1407-9023, Jordan, Jens, Dworak, Markus, Merkel, Tobias and Burnstock, Geoffrey (2019). Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts. Pharmacol. Ther., 194. S. 132 - 145. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 0163-7258

Full text not available from this repository.

Abstract

Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of cardiac metabolism has therefore become an attractive clinical target. Cardiac metabolism is based on the integration of adenosine triphosphate (ATP) production and utilization pathways. ATP itself impacts the heart not only by providing energy, but also represents a central element in the purinergic signaling pathway, which has received considerable attention in recent years. Furthermore, novel drugs that have received interest in HF include angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors, whose favorable cardiovascular profile has been at least partly attributed to their effects on metabolism. This review, describes the major metabolic pathways and concepts of the healthy heart (including fatty acid oxidation, glycolysis, Krebs cycle, Randle cycle, and purinergic signaling) and their dysregulation in the progression to HF (including ketone and amino acid metabolism). The cardiac implications of HF comorbidities, including metabolic syndrome, diabetes mellitus and cachexia are also discussed. Finally, the impact of current HF and diabetes therapies on cardiac metabolism pathways and the relevance of this knowledge for current clinical practice is discussed. Targeting cardiac metabolism may have utility for the future treatment of patients with HF, complementing current approaches. (C) 2018 Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Birkenfeld, Andreas L. UNSPECIFIED orcid.org/0000-0003-1407-9023 UNSPECIFIED Jordan, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Dworak, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkel, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Burnstock, Geoffrey UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-158021
DOI:	10.1016/j.pharmthera.2018.08.015
Journal or Publication Title:	Pharmacol. Ther.
Volume:	194
Page Range:	S. 132 - 145
Date:	2019
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	0163-7258
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED-RECEPTOR-GAMMA; CARDIAC NATRIURETIC PEPTIDES; LEFT-VENTRICULAR FUNCTION; KETONE-BODY METABOLISM; FATTY-ACID-METABOLISM; FAILING HUMAN HEART; LATE SODIUM CURRENT; ADENOSINE A(1); DOUBLE-BLIND; SUBSTRATE METABOLISM Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15802