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

Vogel, O.; Jirkof, P.; Baum, O.; Jakob, P.; Rieger, G.; Gubser, M.; Brock, M.; Gianella, M.; Gassmann, M.; Klohs, J.; Arras, M.; Samillan-Soto, V.; Gorr, T.A.; Hoppeler, H.; Vogel, J.; Schuler, B.; Born, W.; Fischer, J.A.; Cesarovic, N.

dc.contributor.author	Schuler, B.
dc.contributor.author	Rieger, G.
dc.contributor.author	Gubser, M.
dc.contributor.author	Arras, M.
dc.contributor.author	Gianella, M.
dc.contributor.author	Vogel, O.
dc.contributor.author	Jirkof, P.
dc.contributor.author	Cesarovic, N.
dc.contributor.author	Klohs, J.
dc.contributor.author	Jakob, P.
dc.contributor.author	Brock, M.
dc.contributor.author	Gorr, T.A.
dc.contributor.author	Baum, O.
dc.contributor.author	Hoppeler, H.
dc.contributor.author	Samillan-Soto, V.
dc.contributor.author	Gassmann, M.
dc.contributor.author	Fischer, J.A.
dc.contributor.author	Born, W.
dc.contributor.author	Vogel, J.
dc.date.accessioned	2020-06-10T18:11:36Z
dc.date.available	2020-06-10T18:11:36Z
dc.date.issued	2014
dc.identifier.uri	https://hdl.handle.net/20.500.12866/8022
dc.description.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.	en_US
dc.language.iso	eng
dc.publisher	Wiley
dc.relation.ispartofseries	Acta Physiologica
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	hemoglobin	en_US
dc.subject	Animals	en_US
dc.subject	histology	en_US
dc.subject	adult	en_US
dc.subject	male	en_US
dc.subject	priority journal	en_US
dc.subject	Mice	en_US
dc.subject	controlled study	en_US
dc.subject	oxygen consumption	en_US
dc.subject	article	en_US
dc.subject	phenotype	en_US
dc.subject	genetics	en_US
dc.subject	metabolism	en_US
dc.subject	animal experiment	en_US
dc.subject	animal model	en_US
dc.subject	animal tissue	en_US
dc.subject	nonhuman	en_US
dc.subject	animal	en_US
dc.subject	mouse	en_US
dc.subject	Mice, Knockout	en_US
dc.subject	Motor Activity	en_US
dc.subject	exercise	en_US
dc.subject	drug effects	en_US
dc.subject	physiology	en_US
dc.subject	animal cell	en_US
dc.subject	protein expression	en_US
dc.subject	nuclear magnetic resonance imaging	en_US
dc.subject	in vitro study	en_US
dc.subject	mean arterial pressure	en_US
dc.subject	skeletal muscle	en_US
dc.subject	in vivo study	en_US
dc.subject	knockout mouse	en_US
dc.subject	morphometrics	en_US
dc.subject	motor activity	en_US
dc.subject	exhaustion	en_US
dc.subject	exercise test	en_US
dc.subject	endurance training	en_US
dc.subject	Oxygen Consumption	en_US
dc.subject	collagen type 1	en_US
dc.subject	body fat	en_US
dc.subject	alpha calcitonin gene related peptide	en_US
dc.subject	Athlete's heart	en_US
dc.subject	basal metabolic rate	en_US
dc.subject	blood volume	en_US
dc.subject	calcitonin gene related peptide	en_US
dc.subject	Calcitonin Gene-Related Peptide	en_US
dc.subject	Cardiomegaly, Exercise-Induced	en_US
dc.subject	collagen type 3	en_US
dc.subject	Doping	en_US
dc.subject	Endurance capacity	en_US
dc.subject	exercise induced cardiomegaly	en_US
dc.subject	exercise induced heart hypertrophy	en_US
dc.subject	Exercise performance	en_US
dc.subject	heart hypertrophy	en_US
dc.subject	heart index	en_US
dc.subject	heart muscle cell	en_US
dc.subject	heart ventricle hypertrophy	en_US
dc.subject	muscle cell	en_US
dc.subject	Muscle metaboreflex	en_US
dc.subject	Myocytes, Cardiac	en_US
dc.subject	Physical Conditioning, Animal	en_US
dc.subject	Sport	en_US
dc.title	Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1111/apha.12244
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.01.08
dc.relation.issn	1748-1716