Early Postnatal Cardiac Stress Does Not Influence Ventricular Cardiomyocyte Cell-Cycle Withdrawal

Abstract

Congenital heart disease (CHD) is the most common birth defect. After birth, patients with CHD may suffer from cardiac stress resulting from abnormal loading conditions. However, it is not known how this cardiac burden influences postnatal development and adaptation of the ventricles. To study the transcriptional and cell-cycle response of neonatal cardiomyocytes to cardiac stress, we used a genetic mouse model that develops left ventricular volume overload within 2 weeks after birth. The increased volume load caused upregulation of the cardiac stress marker Nppa in the left ventricle and interventricular septum as early as 12 days after birth. Transcriptome analysis revealed that cardiac stress induced the expression of cell-cycle genes. This did not influence postnatal cell-cycle withdrawal of cardiomyocytes and other cell types in the ventricles as measured by Ki-67 immunostaining.

Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes

“…RNA-sequencing from cardiac nuclei was performed as described previously [28]. 500 pg of RNA was used for cDNA preparation with the Ovation RNA-seq V2 kit (7102-08, Tecan, Leek, The Netherlands).…”

Clonal Tracing of Heart Regeneration

“…The adult mammalian heart is considered to be a postmitotic organ, and various studies have estimated the annual turnover of cardiomyocytes to be around 1–1.5%, which declines with age [ 11 , 12 ]. Earlier methods utilized to study cardiomyocyte proliferation included tracking the expression of proliferation markers, or nucleotide incorporation [ 13 , 14 , 15 , 16 , 17 ]. Immunostaining for markers such as Ki67, phosphorylated histone H3 (PH3), and Aurora B kinase have been used in various studies, but staining for these markers can only reveal cardiomyocytes that are proliferating at a given point in time.…”