title: Systemic, but not cardiomyocyte-specific, deletion of the natriuretic peptide receptor guanylyl cyclase A increases cardiomyocyte number in neonatal mice.
abstract: Guanylyl cyclase A (GC-A), the receptor for atrial and B-type natriuretic peptides, is implicated in the regulation of blood pressure and cardiac growth. We used design-based stereological methods to examine the effect of GC-A inactivation on cardiomyocyte volume, number and subcellular composition in postnatal mice at day P2. In mice with global, systemic GC-A deletion, the cardiomyocyte number was significantly increased, demonstrating that hyperplasia is the main cause for the increase in ventricle weight in these early postnatal animals. In contrast, conditional, cardiomyocyte-restricted inactivation of GC-A had no significant effect on ventricle weight or cardiomyocyte number. The mean volume of cardiomyocytes and the myocyte-related volumes of the four major cell organelles (myofibrils, mitochondria, nuclei and sarcoplasm) were similar between genotypes. Taken together, systemic GC-A deficiency induces cardiac enlargement based on a higher number of normally composed and sized cardiomyocytes early after birth, whereas cardiomyocyte-specific GC-A abrogation is not sufficient to induce cardiac enlargement and has no effect on number, size and composition of cardiomyocytes. We conclude that postnatal cardiac hyperplasia in mice with global GC-A inactivation is provoked by systemic alterations, e.g., arterial hypertension. Direct GC-A-mediated effects in cardiomyocytes seem not to be involved in the regulation of myocyte proliferation at this early stage.
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. schipke.julia@mh-hannover.de.|Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. schipke.julia@mh-hannover.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Schipke
authors.affiliation: Institute of Physiology, University of Würzburg, 97070, Würzburg, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Roloff
authors.affiliation: Institute of Physiology, University of Würzburg, 97070, Würzburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. muehlfeld.christian@mh-hannover.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625, Hannover, Germany. muehlfeld.christian@mh-hannover.de.|Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. muehlfeld.christian@mh-hannover.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D017353:Gene Deletion; D005838:Genotype; D006965:Hyperplasia; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D017461:Receptors, Atrial Natriuretic Factor / Q000172:deficiency* / Q000235:genetics
chemical_list: D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A
keywords: Atrial natriuretic peptide; Cardiomyocyte number; Guanylyl cyclase A; Hyperplasia; Hypertrophy