Increased length-dependent activation of human engineered heart tissue after chronic α_1A-adrenergic agonist treatment: testing a novel heart failure therapy.

ABSTRACT: Chronic stimulation of cardiac α_1A-adrenergic receptors (α_1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. Human engineered heart tissues (EHTs) provide a means of quantifying the effects of chronic α_1A-AR stimulation on human cardiomyocyte physiology. EHTs were created from thin slices of decellularized pig myocardium seeded with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and fibroblasts. With a paired experimental design, EHTs were cultured for 3 wk, mechanically tested, cultured again for 2 wk with α_1A-AR agonist A61603 (10 nM) or vehicle control, and retested after drug washout for 24 h. Separate control experiments determined the effects

SUBMITTER: Rupert C 

PROVIDER: S-EPMC9886349 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature