Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation.

• Keywords
• ROCK, cardiomyocyte proliferation, compaction, conduction, mouse embryonic heart, myocardial trabeculae, ventricular wall,
• Publication type
• Journal Article MeSH

The heart is capable of extensive adaptive growth in response to the demands of the body. When the heart is confronted with an increased workload over a prolonged period, it tends to cope with the situation by increasing its muscle mass. The adaptive growth response of the cardiac muscle changes significantly during phylogenetic and ontogenetic development. Cold-blooded animals maintain the ability for cardiomyocyte proliferation even in adults. On the other hand, the extent of proliferation during ontogenetic development in warm-blooded species shows significant temporal limitations: whereas fetal and neonatal cardiac myocytes express proliferative potential (hyperplasia), after birth proliferation declines and the heart grows almost exclusively by hypertrophy. It is, therefore, understandable that the regulation of the cardiac growth response to the increased workload also differs significantly during development. The pressure overload (aortic constriction) induced in animals before the switch from hyperplastic to hypertrophic growth leads to a specific type of left ventricular hypertrophy which, in contrast with the same stimulus applied in adulthood, is characterized by hyperplasia of cardiomyocytes, capillary angiogenesis and biogenesis of collagenous structures, proportional to the growth of myocytes. These studies suggest that timing may be of crucial importance in neonatal cardiac interventions in humans: early definitive repairs of selected congenital heart disease may be more beneficial for the long-term results of surgical treatment.

• Keywords
• adaptation to overload, adaptive growth response, cardiac development, hyperplasia, hypertrophy, phylogeny, postnatal ontogeny,
• Publication type
• Journal Article MeSH
• Review MeSH

Fibroblast growth factor 21 (FGF21) is one of the members of endocrine arm of FGF family. Its actions as a glucose and lipids metabolism regulator are widely known. Although the mechanism of FGF21 action in kidneys is still under investigation, FGF21 was considered as a marker of early kidney function decline. While many researchers focused on adult subjects in this matter, there are no data regarding children. Therefore, we have investigated the relationship between plasma or urine FGF21 levels and kidney function in a group of 42 pediatric patients with chronic kidney disease (CKD). Anthropometrical parameters and blood pressure were taken, routine biochemical tests were performed. The concentration of FGF21 in serum and urine was determined by enzyme immunoassay. The results revealed significantly higher serum FGF21 concentration among children from CKD group. However, serum FGF21 level was not related to gender, proteinuria, eGFR or renal replacement therapy. Urine FGF21 concentration correlated negatively with albuminuria and positively with eGFR. Documented negative correlation of FGF21 fractional excretion and eGFR is not enough to support the role of FGF21 as a biomarker for predicting kidney disease progression in children and adolescents. Other mechanisms including local kidney FGF21 production or enhanced excretion due to higher extrarenal production may result in higher urine FGF21 concentrations.

• MeSH
• Biomarkers blood   urine   MeSH
• Renal Insufficiency, Chronic blood   pathology   urine   MeSH
• Child MeSH
• Fibroblast Growth Factors blood   urine   MeSH
• Glomerular Filtration Rate MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Disease Progression MeSH
• Case-Control Studies MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• FGF21 protein, human MeSH Browser
• Fibroblast Growth Factors MeSH