Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However, the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated in vitro using human vascular smooth muscle cells (TG/HA-VSMCs) as one of the cell types crucial in the development of restenosis. PDT-induced cell death was studied on many levels, including annexin V staining, measurement of the generation reactive oxygen species (ROS) and caspase-3 activity, and assessment of changes in mitochondrial membrane potential and fragmentation of DNA. Photosensitization of TG/HA-VSMCs with a 170 μM of chlorin e6 and subsequent illumination with the light of a 672-nm diode laser (2 J/cm2) resulted in the generation of ROS, a decrease in cell membrane polarization, caspase-3 activation, as well as DNA fragmentation. Interestingly, the latter two apoptotic events could not be observed in photosensitized and illuminated NIH3T3 fibroblasts, suggesting different outcomes of the model of PDT in various types of cells. The results obtained with human VSMCs show that chlorin e6 may be useful in the PDT of aerial restenosis, but its efficacy still needs to be established in an animal model.
Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase‐2 (MMP‐2). It has been shown that simultaneous inhibition of MMP‐2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML‐7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co‐administration of nitric oxide synthase (NOS) inhibitor (1400W or L‐NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia–reoxygenation (H‐R)‐induced contractile dysfunction of cardiomyocytes. Isolated cardiomyocytes were subjected to 3 min. of hypoxia and 20 min. of reoxygenation in the presence or absence of the inhibitor cocktails. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP‐2 by Doxy (25–100 μM), MLCK by ML‐7 (0.5–5 μM) and NOS by L‐NAME (25–100 μM) or 1400W (25–100 μM) protected myocyte contractility after H‐R in a concentration‐dependent manner. Inhibition of these activities resulted in full recovery of cardiomyocyte contractility after H‐R at the level of highest single‐drug concentration. The combination of subthreshold concentrations of NOS, MMP‐2 and MLCK inhibitors fully protected cardiomyocyte contractility and MLC1 from degradation by MMP‐2. The observed protection with addition of L‐NAME or 1400W was better than previously reported combination of ML‐7 and Doxy. The results of this study suggest that addition of NOS inhibitor to the mixture of inhibitors is better strategy for protecting cardiomyocyte contractility.
The registration of physical signals has long been an important part of cardiological diagnostics. Current technology makes it possible to send large amounts of data to remote locations. Solutions that enable diagnosis and treatment without direct contact with patients are of enormous value, especially during the COVID-19 outbreak, as the elderly require special protection. The most important examples of telemonitoring in cardiology include the use of implanted devices such as pacemakers and defibrillators, as well as wearable sensors and data processing units. The arrythmia detection and monitoring patients with heart failure are the best studied in the clinical setting, although in many instances we still lack clear evidence of benefits of remote approaches vs. standard care. Monitoring for ischemia is less well studied. It is clear however that the economic and organizational gains of telemonitoring for healthcare systems are substantial. Both patients and healthcare professionals have expressed an enormous demand for the further development of such technologies. In addition to these subjects, in this paper we also describe the safety concerns associated with transmitting and storing potentially sensitive personal data.
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