Downregulation of the muscle-specific microRNA-1 (miR-1) mediates the induction of pathologic cardiac hypertrophy. Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT). However, it is still unknown whether miR-1 and Cx43 are interconnected in the pro-arrhythmic context of hypertrophy. Thus, in this study we investigated whether a reduction in the extent of cardiac hypertrophy could limit the pathological electrical remodeling of Cx43 and the onset of VT by modulating miR-1 levels. Wistar male rats underwent mechanical constriction of the ascending aorta to induce pathologic left ventricular hypertrophy (LVH) and afterwards were randomly assigned to receive 10mg/kg valsartan, VAL (LVH+VAL) delivered in the drinking water or placebo (LVH) for 12 weeks. Sham surgery was performed for control groups. Programmed ventricular stimulation reproducibly induced VT in LVH compared to LVH+VAL group. When compared to sham controls, rats from LVH group showed a significant decrease of miR-1 and an increase of Cx43 expression and its ERK1/2-dependent phosphorylation, which displaces Cx43 from the gap junction. Interestingly, VAL administration to rats with aortic banding significantly reduced cardiac hypertrophy and prevented miR-1 down-regulation and Cx43 up-regulation and phosphorylation. Gain- and loss-of-function experiments in neonatal cardiomyocytes (NCMs) in vitro confirmed that Cx43 is a direct target of miR-1. Accordingly, in vitro angiotensin II stimulation reduced miR-1 levels and increased Cx43 expression and phosphorylation compared to un-stimulated NCMs. Finally, in vivo miR-1 cardiac overexpression by an adenoviral vector intra-myocardial injection reduced Cx43 expression and phosphorylation in mice with isoproterenol-induced LVH. In conclusion, miR-1 regulates Cx43 expression and activity in hypertrophic cardiomyocytes in vitro and in vivo. Treatment of pressure overload-induced myocyte hypertrophy reduces the risk of life-threatening VT by normalizing miR-1 expression levels with the consequent stabilization of Cx43 expression and activity within the gap junction.

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Background— Ticagrelor outperforms clopidogrel in preventing cardiovascular events in acute coronary syndrome. Despite the inclusion of a loading dose in the Platelet Inhibition and Patient Outcomes (PLATO) trial for all patients randomized to ticagrelor, it may not be necessary in patients receiving ongoing clopidogrel therapy. The aim of the present study was to assess whether a ticagrelor loading dose is associated with a further platelet inhibition during the switch from clopidogrel to ticagrelor in patients with acute coronary syndrome receiving ongoing antiplatelet treatment. Methods and Results— Fifty patients with acute coronary syndrome receiving aspirin and clopidogrel treatment were randomly assigned to a starting dose of ticagrelor (group 1, 90 mg; group 2, 180 mg). Platelet aggregation was measured using multiple electrode aggregometry and standard light transmission aggregometry just before the switch and at 2, 6, 24, and 72 hours. No relevant difference in platelet aggregation was observed between the 2 study arms at baseline ( P =0.256). Residual platelet aggregation was significantly reduced in both arms 2 hours after the first administration of ticagrelor ( P <0.001 for both), with no difference in aggregation between groups (multiple electrode aggregometry, 17.6±7.2 versus 18.1±6 U; P =0.281). Similar results were observed with LTA. Conclusions— Switching from clopidogrel to ticagrelor without a reloading dose is feasible, and it does not hinder platelet aggregation inhibition in patients with acute coronary syndrome. Further prospective studies are needed to assess the clinical relevance of our findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01795820.

Currently, the only efficient way to prevent human Cytomegalovirus (HCMV) infection in pregnancy is primary prophylaxis through hygienic measures. So, we evaluated knowledge of HCMV and its prevention in a group of pregnant women. An anonymous questionnaire with multiple-choice answers was administered to all pregnant women who were followed up at the Obstetrics and Gynecology Unit of “Pugliese-Ciaccio Hospital,” a third-level hospital in Catanzaro (Southern Italy), from November 2015 to March 2016. Previously prescribed serology results for HCMV were also evaluated. Three hundred and fifty women participated in the study and the results clearly demonstrated that knowledge of pregnant women about HCMV is poor. Moreover, prescribed screening procedures need to be optimized, since one out of three pregnant women has not been tested for HCMV or the screening was not performed adequately. For this reason, it is important to implement informative campaign in both pregnant women and providing physicians.