BackgroundThe efficacy of treating acute myocardial ischemic damages depends, to a large extent, on the development of technologies for predicting their course and outcome. The aim of this paper was to explore whether it would be possible to consider the content of free circulating mitochondrial DNA as a danger-associated molecular pattern for assessing the probability of death from myocardial infarction.MethodsWe have analyzed the clinical outcomes based on discharge summaries and autopsy reports obtained in the course of the PROTOCOL observational trial. This study was approved by the Irkutsk Scientific Center of Surgery and Traumatology ethics committee (protocol No. 3, 10.08.2015). To examine whether the assessment of the level of free circulating mtDNA in acute coronary syndrome can help predicting clinical outcomes, all patients were divided into two groups: group 1, involving those who survived during 30 days after hospitalization, and group 2, involving those who died during this time. A quantitative analysis of the free circulating mtDNA was conducted using the PCR method in situ.ResultsThe analysis showed that in patients who survived the level of freely circulating mtDNA (36.0 copies/ml) was 164 times lower than in those who died (5900 copies/ml, p = 0.049). It should be mentioned that according to the logistic regression analysis, the probability of death of patients with the increased level of blood plasma mtDNA (more than 4000 copies/ml) is 50%.ConclusionsThus, the PROTOCOL observational trial proved that the increase in the content of free circulating mtDNA in blood is a predictor of lethal outcome in patients with acute coronary syndrome. Trial registration The observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.

This review considers the functions of extracellular actin - cell surface bound, associated with extracellular matrix, or freely circulating. The role of this protein in different pathological processes is analyzed: its toxic effects and involvement in autoimmune diseases as an autoantigen. The extracellular actin clearance system and its role in protection against the negative effects of actin are characterized. Levels of free-circulating actin, anti-actin immunoglobulins, and components of the actin clearance system as prognostic biomarkers for different diseases are reviewed. Experimental approaches to protection against excessive amounts of free-circulating F-actin are discussed.

Changes in the level of blood cell-free circulating mitochondrial DNA were examined during experimental adrenaline-induced myocardial injury in rats. The amount of mitochondrial DNA in the blood was significantly elevated at 48 and 72 h after subcutaneous injection of adrenaline solution, and it was accompanied by development of multiple small-focal myocardial ischemia. This suggests that the measured level of blood cell-free circulating mitochondrial DNA might be used as a biomarker of acute myocardial ischemia.

We studied the relationship between diffusion transport and morphological and microstructural organization of extracellular matrix of human intervertebral disk. Specimens of the lumbar intervertebral disks without abnormalities were studied ex vivo by diffusion-weighed magnetic resonance imaging, histological and immunohistochemical methods, and electron microscopy. Distribution of the diffusion coefficient in various compartments of the intervertebral disk was studied. Significant correlations between diffusion coefficient and cell density in the nucleus pulposus, posterior aspects of annulus fibrosus, and endplate at the level of the posterior annulus fibrosus were detected for each disk. In disks with nucleus pulposus diffusion coefficient below 15×10 mm/sec, collagens X and XI were detected apart from aggrecan and collagens I and II. The results supplement the concept on the relationship between the microstructure and cell composition of various compartments of the intervertebral disk and parameters of nutrient transport.

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