Numerous studies have reported correlations between plasma microRNA signatures and cardiovascular disease. MicroRNA-133a (Mir-133a) has been researched extensively for its diagnostic value in acute myocardial infarction (AMI). While initial results seemed promising, more recent studies cast doubt on the diagnostic utility of Mir-133a, calling its clinical prospects into question. Here, the diagnostic potential of Mir-133a was analyzed using data from multiple papers. Medline, Embase, and Web of Science were systematically searched for publications containing “Cardiovascular Disease”, “MicroRNA”, “Mir-133a” and their synonyms. Diagnostic performance was assessed using area under the summary receiver operator characteristic curve (AUC), while examining the impact of age, sex, final diagnosis, and time. Of the 753 identified publications, 9 were included in the quantitative analysis. The pooled AUC for Mir-133a was 0.73. Analyses performed separately on studies using healthy vs. symptomatic controls yielded pooled AUCs of 0.89 and 0.68, respectively. Age and sex were not found to significantly affect diagnostic performance. Our findings indicate that control characteristics and methodological inconsistencies are likely the causes of incongruent reports, and that Mir-133a may have limited use in distinguishing symptomatic patients from those suffering AMI. Lastly, we hypothesized that Mir-133a may find a new use as a risk stratification biomarker in patients with specific subsets of non-ST elevation myocardial infarction (NSTEMI).

BACKGROUND: The study of atrial arrhythmias has been hampered by the lack of anatomically relevant human cardiac tissue models and by the inability to perform targeted, functional perturbations in such models. METHODS: To engineer anatomically relevant light-sensitive atrial chambers, we combined human pluripotent stem cells, differentiation protocols yielding atrial and sinoatrial nodal cells, rat heart decellularization/recellularization processes, and optogenetics tools. RESULTS: Immunostaining for chamber-specific cardiomyocyte markers, optical action potential recordings, and the response to atrial-specific pharmacology confirmed the atrial-specific identity of the recellularized engineered tissue. Histological examination verified the preservation of the macroscopic and microscopic atrial architecture of the engineered atria. Optical mapping showed the ability of seeded human pluripotent stem cell–derived sinoatrial nodal cells at the correct anatomic site to serve as a biological pacemaker. Adenoviral transduction and transgenic human pluripotent stem cells were used to express the light-sensitive channels, ChR2 (channelrhodopsin-2) or CoChR ( chloromonas oogama channelrhodopsin), in the bioengineered atria, allowing optogenetic pacing and programmed stimulation. Reentrant arrhythmias could be induced and optically mapped in the bioengineered atrial tissue models, demonstrating the ability to recapitulate and provide insights into different atrial fibrillation mechanisms. These arrhythmias could be terminated by localized (focal or linear) or diffused optogenetic silencing (optogenetic cardioversion). CONCLUSIONS: A novel, light-controllable, bioengineered humanized biatrial tissue model was established and could be used to model different atrial arrhythmias, for drug testing, for disease modeling, and for evaluation of novel therapeutic interventions such as biological pacemaking and optogenetic interventions.