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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, O; Hoppeler, H; 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):107-121.

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Physiology
Language:German
Date:2014
Deposited On:20 May 2014 14:59
Last Modified:02 Nov 2024 04:32
Publisher:Wiley-Blackwell
ISSN:1748-1708
Additional Information:This is the accepted version of the following article: Acta Physiologica (2014), 211(1):107-121, which has been published in final form at dx.doi.org/10.1111/apha.12244
OA Status:Green
Publisher DOI:https://doi.org/10.1111/apha.12244
PubMed ID:24479375

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