Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice.

Schuler, B; Rieger, G; Gubser, M; Arras, M; Gianella, M; Vogel, O; Jirkof, P; Cesarovic, N; Klohs, J; Jakob, P; Brock, M; Gorr, T A; Baum, Oliver; Hoppeler, Hans-Heinrich; Samillan-Soto, V; Gassmann, M; Fischer, J A; Born, W; Vogel, J (2014). Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice. Acta physiologica, 211(1), pp. 107-121. Blackwell Publishing 10.1111/apha.12244

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AIM It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. METHODS The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. RESULTS While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. CONCLUSIONS Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Baum, Oliver and Hoppeler, Hans-Heinrich

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1748-1708

Publisher:

Blackwell Publishing

Language:

English

Submitter:

Annette Draeger

Date Deposited:

03 Feb 2015 15:58

Last Modified:

12 Nov 2015 09:32

Publisher DOI:

10.1111/apha.12244

PubMed ID:

24479375

Uncontrolled Keywords:

athlete's heart, doping, endurance capacity, exercise performance, muscle metaboreflex, sport

BORIS DOI:

10.7892/boris.62801

URI:

https://boris.unibe.ch/id/eprint/62801

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