Flagellin-Induced Immune Response in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Pathogen-associated molecular patterns (PAMPs) are involved in the pathogenesis of septic cardiomyopathy through a toll-like receptor (TLR)-mediated immune response. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can reflect the innate immune abilities of cardiomyocytes. Therefore, hiPSC-CMs may provide an attractive tool with which to study PAMP-induced alterations in cardiomyocytes. HiPSC-CMs from two different healthy donors were exposed to the PAMP flagellin (FLA) at different doses and exposure times. Alterations in the expression levels of distinct inflammation-associated cytokines, intracellular inflammation pathways including TLR5 downstream signaling, reactive oxygen species levels and surface antigen composition were assessed using PCR, ELISA and FACS techniques. Higher doses of flagellin increased the expression levels of inflammation-associated cytokines like TNFα (p < 0.01) and downstream signaling molecules like caspase-8 (p < 0.05). TLR5 expression (p < 0.01) and TLR5 fluorescence proportion (p < 0.05) increased in hiPSC-CMs after prolonged FLA exposure. FLA-induced innate immune response processes in cardiomyocytes might be detectable with an hiPSC-CMs-based in vitro model.

Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease-A Translational Perspective.

Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects "beyond thrombosis", including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.

Prognostic value of beta-blocker doses in patients with ventricular tachyarrhythmias.

The study investigates the prognostic significance of beta-blocker (BB) dose in patients with ventricular tachyarrhythmias. Limited data regarding the prognostic impact of BB dose in ventricular tachyarrhythmias is available. A large retrospective registry was used including consecutive patients on BB treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Discharge BB doses were grouped as > 0-12.5%, > 12.5-25%, > 25-50%, and > 50% according to doses used in randomized trials. The primary endpoint was all-cause mortality at three years. Secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias and appropriate ICD therapies) and cardiac rehospitalization. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied for statistics. A total of 1313 patients with BB were included; most patients were discharged with > 25-50% of BB target dose (59%). At three years, > 12.5-25% of BB target dose was associated with improved long-term mortality as compared to the > 0-12.5% group (HR = 0.489; 95% CI 0.297-0.806; p = 0.005), whereas higher BB doses did not improve survival (> 25-50%: HR = 0.849; p = 0.434; > 50%: HR = 0.735; p = 0.285). In contrast, the composite endpoint and risk of rehospitalization were not affected by BB target dose. In conclusion, > 12.5-25% of BB target dose is associated with best long-term survival among patients with ventricular tachyarrhythmias. In contrast, risk of the composite arrhythmic endpoint and risk of cardiac rehospitalization were not affected by BB dose.