Abstract:The aim of the present investigation is to study the level of plasma mtDNA as a potential marker of cardiomyocyte damage in 2 and 4 h after subcutaneous injection of adrenaline and during the formed morphological alterations of the myocardium (3 days). Methods. Real time PCR. Male Wistar rats were used as the experimental animals. Results. It was shown that during the increase in the activity of cytolysis biomarkers, at the first hours after adrenaline injection, no reliable increase is observed in the level o… Show more
“…It was already explored the dynamics of the level of free circulating blood plasma mtDNA in acute myocardial ischemia and observed the increase in blood plasma mtDNA concentration [5–7]. Recently, we found the raise of concentration of free circulating mitochondrial DNA in blood after injection of adrenaline that caused the development of multiple small focal myocardial ischemia in Wistar rats [8, 9]. Recent observations [10] reveal the molecular mechanism behind the development of acute heart failure in animal models, where mitochondrial DNA is an important pathogenic factor.…”
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.
“…It was already explored the dynamics of the level of free circulating blood plasma mtDNA in acute myocardial ischemia and observed the increase in blood plasma mtDNA concentration [5–7]. Recently, we found the raise of concentration of free circulating mitochondrial DNA in blood after injection of adrenaline that caused the development of multiple small focal myocardial ischemia in Wistar rats [8, 9]. Recent observations [10] reveal the molecular mechanism behind the development of acute heart failure in animal models, where mitochondrial DNA is an important pathogenic factor.…”
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.
“…Тем не менее, в настоящее время не выявлены биомаркеры, связующие со-стояние митохондрий и процессы гибели клетки при инфаркте миокарда и атеросклерозе. Одним из перспективных показателей разрушения, стрессиро-вания клеток и, возможно, состояния митохондрий является свободно циркулирующая митохондриаль-ная ДНК (мтДНК) крови [1,4,7], которую относят к «молекулярным паттернам риска» (danger associated molecular patterns, DAMPs) [8]. Таким образом, высо-кую актуальность для разработки диагностических и лечебных технологий представляет изучение данных цитологических и молекулярных показателей на ран-них сроках развития дислипопротеидемии, а также в динамике острого ишемического повреждения мио-карда, что явилось целью настоящего исследования.…”
ВВЕДЕНИЕНа сегодняшний день инфаркт миокарда (одно из осложнений дислипопротеидемии и атеросклероза коронарных сосудов) является основной причиной смертности населения индустриально развитых стран. Совершенствование технологий диагностики данных заболеваний во многом предопределяет эф-фективность методов их профилактики и лечения [6]. Важным фактором развития дислипопротеидемии является избыточное накопление в клетках печени липидных капель, способных повреждать органеллы, в первую очередь митохондрии [5]. Известна ключе-вая роль дисфункции митохондрий кардиомиоцитов в развитии повреждений миокарда после воздействия ишемии/реперфузии [2]. Тем не менее, в настоящее время не выявлены биомаркеры, связующие со-стояние митохондрий и процессы гибели клетки при инфаркте миокарда и атеросклерозе. Одним из перспективных показателей разрушения, стрессиро-вания клеток и, возможно, состояния митохондрий является свободно циркулирующая митохондриаль-ная ДНК (мтДНК) крови [1,4,7], которую относят к «молекулярным паттернам риска» (danger associated molecular patterns, DAMPs) [8]. Таким образом, высо-кую актуальность для разработки диагностических и лечебных технологий представляет изучение данных цитологических и молекулярных показателей на ран-них сроках развития дислипопротеидемии, а также в динамике острого ишемического повреждения мио-карда, что явилось целью настоящего исследования.
МАТЕРИАЛЫ И МЕТОДЫДислипопротеидемию вызывали атерогенной диетой (350 мг холестерина на 1 кг веса животного
In recent decades, it has become evident that the condition for normal functioning of mitochondria in higher eukaryotes is the presence of membrane transport systems of macromolecules (proteins and nucleic acids). Natural competence of the mitochondria in plants, animals, and yeasts to actively uptake DNA may be directly related to horizontal gene transfer into these organelles occurring at much higher rate compared to the nuclear and chloroplast genomes. However, in contrast with import of proteins and tRNAs, little is known about the biological role and molecular mechanism underlying import of DNA into eukaryotic mitochondria. In this review, we discuss current state of investigations in this area, particularly specificity of DNA import into mitochondria and its features in plants, animals, and yeasts; a tentative mechanism of DNA import across the mitochondrial outer and inner membranes; experimental data evidencing several existing, but not yet fully understood mechanisms of DNA transfer into mitochondria. Currently available data regarding transport of informational macromolecules (DNA, RNA, and proteins) into the mitochondria do not rule out that the mechanism of protein and tRNA import as well as tRNA and DNA import into the mitochondria may partially overlap.
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