1. Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice
- Author
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Nikola Cesarovic, Margarete Arras, M. Gianella, Hans Hoppeler, G. Rieger, Max Gassmann, Thomas A. Gorr, V. Samillan-Soto, Oliver Baum, Jan A. Fischer, Matthias Brock, P. Jakob, M. Gubser, B. Schuler, Johannes Vogel, Paulin Jirkof, Jan Klohs, Olga Vogel, Walter Born, University of Zurich, and Vogel, J
- Subjects
Physiology ,Blood volume ,animal cell ,heart hypertrophy ,Muscle hypertrophy ,10052 Institute of Physiology ,Mice ,endurance training ,Muscle metaboreflex ,Doping ,Myocyte ,genetics ,animal ,Athlete's heart ,Myocytes, Cardiac ,Cardiomegaly, Exercise-Induced ,nuclear magnetic resonance imaging ,Receptor ,Sport ,Mice, Knockout ,heart ventricle hypertrophy ,exercise ,morphometrics ,purl.org/pe-repo/ocde/ford#3.01.08 [https] ,adult ,exercise induced cardiomegaly ,article ,11359 Institute for Regenerative Medicine (IREM) ,Exercise performance ,10081 Institute of Veterinary Physiology ,oxygen consumption ,muscle cell ,body fat ,blood volume ,medicine.anatomical_structure ,priority journal ,10076 Center for Integrative Human Physiology ,calcitonin gene related peptide ,10209 Clinic for Cardiology ,mean arterial pressure ,heart index ,10178 Clinic for Pneumology ,medicine.medical_specialty ,Mean arterial pressure ,in vitro study ,exercise induced heart hypertrophy ,phenotype ,Calcitonin Gene-Related Peptide ,animal experiment ,exercise test ,heart muscle cell ,610 Medicine & health ,Motor Activity ,Calcitonin gene-related peptide ,animal tissue ,histology ,in vivo study ,collagen type 3 ,Oxygen Consumption ,male ,Physical Conditioning, Animal ,Internal medicine ,exhaustion ,medicine ,Animals ,controlled study ,skeletal muscle ,protein expression ,mouse ,collagen type 1 ,nonhuman ,Endurance capacity ,business.industry ,animal model ,Skeletal muscle ,1314 Physiology ,hemoglobin ,medicine.disease ,Endocrinology ,10022 Division of Surgical Research ,drug effects ,Heart failure ,physiology ,basal metabolic rate ,570 Life sciences ,biology ,knockout mouse ,business ,metabolism ,alpha calcitonin gene related peptide - 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.
- Published
- 2014