BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a rare but deadly form of human congenital heart disease, most likely of diverse etiologies. Hemodynamic alterations such as those resulting from premature foramen ovale closure or aortic stenosis are among the possible pathways. METHODS: The information gained from studies performed in the chick model of HLHS is reviewed. Altered hemodynamics leads to a decrease in myocyte proliferation causing hypoplasia of the left heart structures and their functional changes. CONCLUSIONS: Although the chick phenocopy of HLHS caused by left atrial ligation is certainly not representative of all the possible etiologies, it provides many useful hints regarding the plasticity of the genetically normal developing myocardium under altered hemodynamic loading leading to the HLHS phenotype, and even suggestions on some potential strategies for prenatal repair.

• Klíčová slova
• embryonic myocardium, hemodynamic alteration, left atrial ligation, left ventricular hypoplasia, myocyte proliferation,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The adenylyl cyclase (AC) signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED) 8 significantly downregulated (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development.

• MeSH
• adenylátcyklasy biosyntéza   genetika   MeSH
• antiarytmika aplikace a dávkování   MeSH
• karbazoly aplikace a dávkování   MeSH
• karvedilol MeSH
• kur domácí genetika   růst a vývoj   MeSH
• kuřecí embryo MeSH
• metoprolol aplikace a dávkování   MeSH
• myokard enzymologie   MeSH
• propanolaminy aplikace a dávkování   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• srdce účinky léků   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenylátcyklasy MeSH
• adenylyl cyclase type V MeSH Prohlížeč
• antiarytmika MeSH
• karbazoly MeSH
• karvedilol MeSH
• metoprolol MeSH
• propanolaminy MeSH