Nanoparticle-Based Modification of the DNA Methylome: A Therapeutic Tool for Atherosclerosis?

Cardiovascular epigenomics is a relatively young field of research, yet it is providing novel insights into gene regulation in the atherosclerotic arterial wall. That information is already pointing to new avenues for atherosclerosis (AS) prevention and therapy. In parallel, advances in nanoparticle (NP) technology allow effective targeting of drugs and bioactive molecules to the vascular wall. The partnership of NP technology and epigenetics in AS is just beginning and promises to produce novel exciting candidate treatments. Here, we briefly discuss the most relevant recent advances in the two fields. We focus on AS and DNA methylation, as the DNA methylome of that condition is better understood in comparison with the rest of the cardiovascular disease field. In particular, we review the most recent advances in NP-based delivery systems and their use for DNA methylome modification in inflammation. We also address the promises of DNA methyltransferase inhibitors for prevention and therapy. Furthermore, we emphasize the unique challenges in designing therapies that target the cardiovascular epigenome. Lastly, we touch the issue of human exposure to industrial NPs and its impact on the epigenome as a reminder of the undesired effects that any NP-based therapy must avoid to be apt for secondary prevention of AS.

The impact of exogenous constitutional obesity on the systemic circulation in COVID-19 patients

Актуальность: ожирение является одной из самых распространенных в мире причин развития сопутствующих заболеваний. у человека. В настоящий момент проблема СOVID-19 приводит к развитию и обострению сердечно-сосудистой патологии, сопровождающейся изменениями гемодинамики. Цель исследования - оценка зависимости изменений гемодинамики у пациентов с COVID-19 от алиментарно-конституционального ожирения. Методика. Исследование выполнено у 73 пациентов обоего пола с внебольничной полисегментарной вирусно-бактериальной пневмонией на фоне СOVID-19. Пациенты были разделены на 3 группы по индексу массы тела. В 1-ю группу вошли пациенты без избытка массы тела, 2-ю составили пациенты с избыточной массой тела, 3-ю - с ожирением 1 степени. Использован комплекс аппаратно-программного неинвазивного исследования центральной гемодинамики методом объемной компрессионной осциллометрии «КАП ЦГ осм- «Глобус» (Россия). Результаты. У пациентов с СOVID-19, страдающих ожирением I степени (30,0 - 34,9 кг/м2). выявлено статистически значимое снижение сердечного индекса относительно лиц с нормальной массой тела (на 10,8%, p=0,010). Пациенты с избытком массы тела имели более высокое диастолическое давление (на 10,5%, p=0,011) Показатель периферического сосудистого сопротивления у пациентов с СOVID-19 без избыточной массы тела был на 16.5% ниже, чем у пациентов с ожирением 1 степени. Удельное периферическое сопротивление сосудов у пациентов 1-й группы было на 10.3% меньше, чем у пациентов с избыточной массой тела. Податливость сосудистой стенки у пациентов 1-й группы была ниже на 22.5%, чем у пациентов с СOVID-19 и ожирением 1 степени. Заключение. У пациентов с внебольничной полисегментарной вирусно-бактериальной пневмонией на фоне СOVID-19 при ожирении 1 степени и избыточной массе тела выявляются значимые изменения гемодинамики относительно больных с нормальной массой тела. Background: Obesity is one of the most common causes of comorbidities worldwide. During the COVID-19 pandemic, development and increasing severity of cardiovascular disorders associated with hemodynamic changes has become increasingly relevant. Aims: The study aimed to evaluate the hemodynamic changes in COVID-19 patients depending on the severity of their exogenous constitutional obesity. Methods. 73 male and female patients with community-acquired polysegmental pneumonia of viral and bacterial origin associated with COVID-19 were enrolled in the study. The patients were allocated to three groups depending on the value of their body mass index (BMI). Group 1 included patients with normal body weight; Group 2 included overweight patients, and Group 3 included patients with grade 1 obesity (BMI 30.0-34.9 kg/m2). The measurements were performed using a technique of volumetric compression oscillometry on a non-invasive hemodynamic monitoring system KAP CG osm (Globus, Russia). Results. COVID-19 patients with grade 1 obesity (BMI 30.0-34.9 kg/m2) demonstrated a statistically significant 10.8% decrease in the cardiac index compared to patients with normal body weight (p=0.010). Overweight patients had 10.5% higher diastolic blood pressure (p=0.011). Peripheral vascular resistance (PVR) in COVID-19 patients with normal body weight was 16.5% lower than in patients with grade 1 obesity. PVR adjusted for body surface area in patients with normal body weight was 10.3% lower than in overweight patients. The compliance of the vascular wall in Group 1 patients was 22.5% lower than in COVID-19 patients with grade 1 obesity. Conclusion. COVID-19 patients with community-acquired, polysegmental pneumonia of viral and bacterial origin demonstrate significant hemodynamic changes compared to patients with normal body weights.

Retrospective analysis of cerebral neurological complications against background of seasonal respiratory viral infections and new coronavirus infection Covid‑19

Based on the example of seasonal epidemics of respiratory viral infections, it is partially possible to model the outcomes of neurological complications from Covid‑19, taking into account the pathogenetic features of the virus effect on the vascular wall and nerve cells. The accumulated experience of doctors of various specialties makes it possible to prevent such life-threatening complications as ACVA, PATE, intoxication, and sepsis. From the first days of the disease, it is necessary to conduct dynamic monitoring of blood rheology, the level of systemic oxygenation, use anticoagulants in preventive doses in patients at the early stages of the disease, conduct therapy aimed at reducing the risk of cytokine storm development.

Pathomorphological markers of blast-induced brain injury

Background. Recently, interest in blast-induced brain injuries has been increasing due to military events and the use of explosive devices in eastern Ukraine. Considering the diagnostic uncertainty regarding the specific signs of brain injury after the distant action of an blast shock wave, the danger of prognostic consequences, the increase of the cases of explosive injury number, we consider that selected for study topic is relevant. Objective. Purpose – determination of pathomorphological changes of the brain after the action of the blast wave. Methods. To solving this purpose, a retrospective analysis of 280 cases of fatal military blast injuries was conducted. We selected 6 cases for microscopic examination of the brain. For histological examination, samples were taken from different parts of the brain. Results. Analysis of 280 deaths due to explosive trauma showed that 58.9% of the dead (165) had a traumatic brain injury, and in 131 cases it was accompanied by fractures of the bones of the vault and the base of the skull. Isolated traumatic brain injury was detected in only 33 cases (11.8%). Age distribution analysis of the dead people showed that 67.5% of the dead were between the ages of 21 and 40. Histopathological analysis of brain samples from the dead allowed to identify the characteristic signs of blast-induced brain injury in the form of diffuse formation of perivascular microhemorrhages with partial or complete separation of the vascular wall from the neuropil. Conclusion. The complex of microscopic signs in the brain, namely, the separation of vascular wall from neuroglia with the formation of perivascular space, fragmentation of these vessels walls, erythrocytes hemolysis, hemorrhage in the newly formed perivascular spaces, are direct evidences of the blast wave action.

Ultrastructural characteristics of the rats laryngeal mucosa and cartilage on the 7 and 14 days of the experimental opioid effect

Background and objective. Our main task was to study the ultrastructural organization of the laryngeal mucosa and cartilage on the seventh and fourteenth day of opioid exposure. Methods. The material for the study were mature, outbred male rats in the number of 32 animals, weighing 80g, aged 4.5 months. Animals were injected intramuscularly with Nalbuphine once a day at the same time (10-11 hours in the morning) for 14 days. The initial dose of Nalbuphine was 8 mg / kg during the first week, 15 mg / kg during the second week of the experimental study. Thus, we created the conditions for chronic opioid exposure. Animals were divided into 3 experimental groups: 1 – control group; 2 - animals that received the drug for 7 days; 3 - animals that received the drug for 14 days). All animals were kept in a vivarium. Animal care, labeling and all other manipulations were carried out taking into account the issues of bioethical norms. Before collecting necropsy material, the animal was removed from the experiment with diethyl ether. The the larynx mucosa and rats cartilage were used as the material for ultrastructural examination. Ultrastructural capsule was prepared according to conventional methods. Results. As a result of experimental opioid exposure at the end of 7 days we found alternative changes in the epithelial cells of different parts of the larynx, dyscirculatory changes in blood vessels of lamina propria and submucosa, as well as the destruction of chondrocytes of hyaline and elastic cartilages. The hemocapillaries of lamina propria and submucosa, especially in the ventricles of the larynx and in the subchondral region, were dilated, overflowing with erythrocytes. In the laryngeal mucosa and submucosal base of the laryngeal ventricles, in addition to the overflow of hemocapillaries with erythrocytes, a moderate accumulation of perivascular transudate was noted. At the end of the 14th day of the experimental opioid effect, a pronounced hemocapillaries injury was found, which was accompanied by an increase in the permeability of the vascular wall. In addition to blood plasma, erythrocytes were visualized in the enlarged lumens of hemocapillaries. The development of degenerative changes of endothelial cells, which were accompanied by inhomogeneous dilation of the tubules of the smooth and granular endoplasmic reticulum, was noted. The main substance of the connective tissue of the mucous membrane and submucosal base, especially around the vessels was impregnated with transudate.

Platelet Deposition Onto Vascular Wall Regulated by Electrical Signal

Platelets deposition at the site of vascular injury is a key event for the arrest of bleeding and for subsequent vascular repair. Therefore, the regulation of platelet deposition onto the injured site during the process of platelet plug formation is an important event. Herein, we showed that electrical signal could regulate the deposition of platelets onto the injured site. On the one hand, the area of platelet deposition was reduced when the cathode of the applied electric field was placed at the injured site beforehand, while it was increased when the anode was at the site. On the other hand, if a cathode was placed at the injured site after the injury, the electrical signal could remove the outer layer of the deposited platelets. Furthermore, an electric field could drive rapid platelet deposition onto the blood vessel wall at the site beneath the anode even in uninjured blood vessels. Platelet deposition could thus be manipulated by externally applied electric field, which might provide a mechanism to drive platelet deposition onto the wall of blood vessels.

ADAMTS Proteins and Vascular Remodeling in Aortic Aneurysms

Extracellular matrix (ECM) in the vascular wall is a highly dynamic structure composed of a set of different molecules such as elastins, collagens, fibronectin (Fn), laminins, proteoglycans, and polysaccharides. ECM undergoes remodeling processes to regulate vascular smooth muscle and endothelial cells’ proliferation, differentiation, and adhesion. Abnormalities affecting the ECM can lead to alteration in cellular behavior and from this, this can conduce to the development of pathologies. Metalloproteases play a key role in maintaining the homeostasis of ECM by mediating the cleavage of different ECM components. There are different types of metalloproteases: matrix metalloproteinases (MMPs), disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondin motifs (ADAMTSs). ADAMTSs have been found to participate in cardiovascular physiology and diseases and specifically in aortic aneurysms. This review aims to decipher the potential role of ADAMTS proteins in the physiopathologic development of Thoracic Aortic Aneurysms (TAA) and Abdominal Aortic Aneurysms (AAA). This review will focus on what is known on the ADAMTS family involved in human aneurysms from human tissues to mouse models. The recent findings on THSD4 (encoding ADAMTSL6) mutations in TAA give a new insight on the involvement of the ADAMTS family in TAA.

EVALUATION OF THE VESSEL AGE BY APPLYING THE ACCELERATION PLETHYSMOGRAM ANALYSIS

В работе приведены понятия жесткости, эластичности и тонуса сосудов, а также же их взаимосвязь с общим состоянием сосудистой стенки. Описан индекс, объединяющий влияние вышеперечисленных факторов на состояние сосудистой системы и дающий представление о возрасте сосудов пациента, а также показана связь этого индекса с возрастом человека. Представлен обзор способов определения возраста сосудов с помощью контурного анализа пульсовой волны. Среди предложенных способов был выделен подход на основе контурного анализа сигнала пульсовой волны, а также ее второй производной. В данном исследовании проводилась разработка алгоритма расчета показателя возраста сосудов (VA), базирующаяся на анализе сигнала и его второй производной. При этом особое внимание уделялось физической интерпретации параметров, входящих в состав расчетной формулы. С помощью представленного алгоритма в группе из трех испытуемых был определен сосудистый возраст. Из анализа полученных результатов было выявлено влияние физиологических факторов на значение возраста сосудов. Предложены методики, позволяющие исключить влияние этих факторов на значения показателя VA и тем самым получить более точные результаты. Также представлены стратегии дальнейшего развития исследований в этом направлении In The paper presents the concepts of rigidity, elasticity and tone of blood vessels, as well as their relationship with the general state of the vascular wall. An index is described that combines the influence of the above factors on the state of the vascular system and gives an idea of the age of the patient's vessels, and also shows the relationship of this index with the age of a person. An overview of the methods for determining the age of blood vessels using the contour analysis of the pulse wave is presented. Among the proposed methods, an approach based on the contour analysis of the pulse wave signal, as well as its second derivative, was singled out. In this study, an algorithm was developed for calculating the indicator of vascular age (VA), based on the analysis of the signal and its second derivative. In this case, special attention was paid to the physical interpretation of the parameters included in the calculation formula. Using the presented algorithm, vascular age was determined in a group of three subjects. From the analysis of the results obtained, the influence of physiological factors on the value of the age of the vessels was revealed. Methods are proposed that allow to exclude the influence of these factors on the values of the VA indicator and thereby obtain more accurate results. Also presented are strategies for the further development of research in this direction