Cardiac hypertrophy is clearly double-edged. Left ventricular hypertrophy is the most important antecedent risk factor for the development of heart failure. Its prevalence in the general population is 1–2 %, but reaches more than 10 % in octogenarians. The model will be useful to investigate novel therapeutic approaches in a simple and fast manner.Īging of the population and better survival of patients affected by coronary heart disease have led to an increasing number of patients with chronic heart failure, the common end stage of virtually all cardiac diseases. Sustained afterload enhancement of EHTs alone is sufficient to induce pathological cardiac remodeling with reduced contractile function and increased glucose consumption. These deleterious effects of afterload enhancement were preventable by endothelin-A, but not endothelin-B receptor blockade. Importantly, afterload-enhanced EHTs exhibited reduced contractile force and impaired diastolic relaxation directly after release of the metal braces. Cardiomyocyte hypertrophy was accompanied by activation of the fetal gene program, increased glucose consumption, and increased mRNA levels and extracellular deposition of collagen-1. Cardiomyocytes in EHTs enlarged by 28.4 % under AE and to a similar extent by ET-1- or PE-stimulation (40.6 or 23.6 %), as determined by dystrophin staining. Endothelin-1 (ET-1)- or phenylephrine (PE)-stimulated EHTs served as positive control for hypertrophy. Control EHTs were handled identically without reinforcement. Serum-free, triiodothyronine-, and hydrocortisone-supplemented medium conditions were established to prevent undefined serum effects. After 2 weeks, the posts were reinforced with metal braces, which markedly increased afterload of the spontaneously beating EHTs. Fibrin-based engineered heart tissue (EHT) was cast between two hollow elastic silicone posts in a 24-well cell culture format. The aim of this study was to develop an experimental model that allows investigating the impact of afterload enhancement (AE) on work-performing heart muscles in vitro. Current in vitro models fall short in deciphering the mechanisms of hypertrophy induced by afterload enhancement. Increased afterload results in ‘pathological’ cardiac hypertrophy, the most important risk factor for the development of heart failure.
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