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Aims: Combined magnetic resonance imaging (MRI) of molecular and morpho-functional changes might prove highly valuable for the elucidation of pathological processes involved in the development of cardiac diseases. Our aim was to test a novel MRI reporter gene for in vivo assessment of the canonical Wnt/β-catenin/TCF pathway activation, an important regulator of post-ischaemic cardiac remodelling. Methods and results: We designed and developed a chimeric construct encoding for both of iron-binding human ferritin heavy chain (hFTH) controlled by the β-catenin-responsive TCF/lymphoid-enhancer binding factor (Lef) promoter and constitutively expressed green fluorescent protein (GFP). It was carried by adeno-associated virus serotype 9 (rAAV9) vectors and delivered to the peri-infarct myocardium of rats subjected to coronary ligation (n = 11). By 1.5 T MRI and a multiecho T2* gradient echo sequence, we detected iron accumulation only in the border zone of the transduced infarcted hearts. In the same cardiac area, post-mortem histological analysis confirmed the co-existence of iron accumulation and GFP. The iron signal was absent when rats (n = 6) were chronically treated with SEN195 (10 mg/kg/day), a small-molecular inhibitor of β-catenin/TCF-dependent gene transcription. Canonical Wnt pathway inhibition attenuated the post-ischaemic remodelling process, as demonstrated by the significant preservation of cardiac function, the 42 ± 1% increase of peri-infarct arteriolar density and 43 ± 3% reduction in infarct scar size compared with untreated animals. Conclusions: The TCF/Lef promoter-hFTH construct is a novel and reliable MRI reporter gene for in vivo detection of the canonical Wnt/β-catenin/TCF activation state in response to cardiac injury and therapeutic interventions. [ABSTRACT FROM AUTHOR]

In recent years, a wealth of studies has identified various molecular species released by cardiac muscle under physiological and pathological conditions that exert local paracrine and/or remote endocrine effects. Conversely, humoral factors, principally produced by organs such as skeletal muscle, kidney, or adipose tissue, may affect the function and metabolism of normal and diseased hearts. Although this cross communication within cardiac tissue and between the heart and other organs is supported by mounting evidence, research on the role of molecular mediators carried by exosomes, microvesicles, and apoptotic bodies, collectively defined as extracellular vesicles (EVs), is at an early stage of investigation. Once released in the circulation, EVs can potentially reach any organ where they transfer their cargo of proteins, lipids, and nucleic acids that exert potent biological effects on recipient cells. Although there are a few cases where such signaling was clearly demonstrated, the results from many other studies can only be tentatively inferred based on indirect evidence obtained by infusing exogenous EVs in experimental animals or by adding them to cell cultures. This area of research is in rapid expansion and most mechanistic interpretations may change in the near future; hence, the present review on the role played by EV-carried mediators in the two-way communication between heart and skeletal muscle, kidneys, bone marrow, lungs, liver, adipose tissue, and brain is necessarily limited. Nonetheless, the available data are already unveiling new, intriguing, and ample scenarios in cardiac physiology and pathophysiology.

Objective . The implantation of intraneural electrodes in amputees has been observed to be effective in providing subjects with sensory feedback. However, this implantation is challenging and time consuming. Surgeons must be especially trained to execute the implantation. Therefore, we aimed at developing a novel peripheral intraneural electrode and insertion mechanism, which could drastically reduce the overall implantation time while achieving a high neural selectivity. Approach. A new insertion method based on hollow microneedles was developed to realize the prompt and effective simultaneous implantation of up to 14 active sites in a transversal manner. Each needle guided two Pt/Ir microwires through the nervous tissue. After the insertion, the microneedles were released, leaving behind the microwires. Each microwire had one active site, which was coated with poly-3,4-ethylenedioxythiophene (PEDOT) to enhance the electrochemical properties. The active sites were characterized by evaluating the impedance, charge storage capacity, and maximum injectable charge. Twelve quick to implant peripheral intraneural electrodes (Q-PINEs) were implanted in four pig sciatic nerves to evaluate the implantation time and neural selectivity. We compared the stimulation of the sciatic nerve with that of its branches. Main results . The average surgical access time was 23 min. The insertion time for 12 electrodes was 6.7 min (std. ±1.6 min). The overall implantation time was reduced by 40.3 min compared to the previously reported values. The Q-PINE system demonstrated a satisfactory performance during in vitro and in vivo characterization. The electrochemical results showed that the PEDOT coating successfully increased the electrochemical parameters of the active sites. Significance. With an average impedance of 1.7 kΩ, a maximum charge level of 76.2 nC could be achieved per active site. EMG recruitment curves showed that 46% of the active sites exhibited selective stimulation of four out of six muscles. The histological analysis indicated that the microwires successfully penetrated the nerve and single fascicles., (Creative Commons Attribution license.)