Disruption of glucocorticoid receptor in cardiomyocytes impaired foetal heart function, though unlike global GR knockout which had 22% reduced ventricular volume, SMGRKO heart size was normal.
Glucocorticoid signaling within cardiomyocytes and vascular smooth muscle is essential for structural and functional maturation of the fetal heart, although heart size regulation involves other pathways.
Glucocorticoids are vital for the structural and functional maturation of foetal organs, yet excessive foetal exposure is detrimental to adult cardiovascular health. To elucidate the role of glucocorticoid signalling in late-gestation cardiovascular maturation, we have generated mice with conditional disruption of glucocorticoid receptor (GR) in cardiomyocytes and vascular smooth muscle cells using smooth muscle protein 22-driven Cre recombinase (SMGRKO mice) and compared them with mice with global deficiency in GR (GR(-/-)). Echocardiography shows impaired heart function in both SMGRKO and GR(-/-) mice at embryonic day (E)17.5, associated with generalized oedema. Cardiac ultrastructure is markedly disrupted in both SMGRKO and GR(-/-) mice at E17.5, with short, disorganized myofibrils and cardiomyocytes that fail to align in the compact myocardium. Failure to induce critical genes involved in contractile function, calcium handling and energy metabolism underpins this common phenotype. However, although hearts of GR(-/-) mice are smaller, with 22% reduced ventricular volume at E17.5, SMGRKO hearts are normally sized. Moreover, while levels of mRNA encoding atrial natriuretic peptide are reduced in E17.5 GR(-/-) hearts, they are normal in foetal SMGRKO hearts. These data demonstrate that structural, functional and biochemical maturation of the foetal heart is dependent on glucocorticoid signalling within cardiomyocytes and vascular smooth muscle, though some aspects of heart maturation (size, ANP expression) are independent of GR at these key sites.
Rog‐Zielinska et al. (Tue,) conducted a other in Foetal heart maturation. Conditional disruption of glucocorticoid receptor (SMGRKO) vs. Global deficiency in GR (GR(-/-)) was evaluated on Heart function, cardiac ultrastructure, and ventricular volume. Disruption of glucocorticoid receptor in cardiomyocytes impaired foetal heart function, though unlike global GR knockout which had 22% reduced ventricular volume, SMGRKO heart size was normal.