Intact Arteries Research Articles

C/D box snoRNA SNORD113-6 guides 2′-O-methylation and protects against site-specific fragmentation of tRNALeu(TAA) in vascular remodeling

C/D box small nucleolar RNAs (snoRNAs) of the DLK1-DIO3 locus are associated with vascular remodeling and cardiovascular disease. None of these snoRNAs has any known targets yet except for one, AF357425/SNORD113-6. We previously showed that this snoRNA targets mRNAs of the integrin signaling pathway and affects arterial fibroblast function. Here, we aimed to identify whether AF357425/SNORD113-6 can also target small RNAs. We overexpressed or inhibited AF357425 in murine fibroblasts and performed small RNA sequencing. Expression of transfer (t)RNA fragments (tRFs) was predominantly regulated. Compared with overexpression, AF357425 knockdown led to an overall decrease in tRFs but with an enrichment in smaller tRFs (<30 nucleotides). We focused on tRNA leucine anti-codon TAA (tRNALeu(TAA)), which has a conserved predicted binding site for AF357425/SNORD113-6. Adjacent to this site, the tRNA is cleaved to form tRFLeu 47–64 in both primary murine and human fibroblasts and in intact human arteries. We show that AF357425/SNORD113-6 methylates tRNALeu(TAA) and thereby prevents the formation of tRFLeu 47–64. Exposing fibroblasts to oxidative or hypoxic stress increased AF357425/SNORD113-6 and tRNALeu(TAA) expression, but AF357425/SNORD113-6 knockdown did not increase tRFLeu 47–64 formation under stress even further. Thus, independent of cellular stress, AF357425/SNORD113-6 protects against site-specific fragmentation of tRNALeu(TAA) via 2′O-ribose-methylation.

Physiological levels of fluid shear stress modulate vascular function through TRPV4 sparklets.

Endothelial calcium (Ca 2+) signaling plays a major role in regulating vasodilation in response to fluid shear stress (FSS) generated by blood flow. Local Ca 2+ influx through single transient receptor potential channel subfamily V member 4 (TRPV4) (termed "sparklets") activated by low concentrations of chemical and biological stimuli has been revealed to modulate vascular function. However, the range in which FSS can initiate TRPV4 sparklets to induce vasodilation is unknown. Here, we assess the activity of TPRV4 sparklets induced by various physiological levels of FSS and investigate the mechanisms involving these Ca 2+ signals in FSS-induced vasodilation. Intact small mesenteric arteries are used for Ca 2+ imaging with a GCaMP2(TRPV4-KO) mouse model and high-speed confocal systems. Markedly increased local Ca 2+ signals are observed in the endothelium under 4-8 dyne/cm 2 FSS, whereas FSS >8 dyne/cm 2 causes global Ca 2+ influx. Further analysis shows that TRPV4 channels form a four-channel group to mediate Ca 2+ sparklets under certain levels of FSS. The large Ca 2+ influx hyperpolarizes endothelial cells by stimulating intermediate (IK)- and small (SK)-conductance Ca 2+-sensitive potassium channels, leading to hyperpolarization of the surrounding smooth muscle cells and ultimately causing endothelium-dependent vasodilation. In conclusion, Ca 2+ influx transits through a small number of endothelial TRPV4 channels opened by certain levels of FSS, which activates the Ca 2+-sensitive IK and SK channels to cause vasodilation.

Features of the pathogenesis and course of myocardial infarction in COVID-19 patients: a descriptive review

The coronavirus disease 2019 (COVID-19) pandemic remains one of the most urgent problems for healthcare professionals due to the variety of non-pulmonary manifestations. Along with the respiratory syndrome in a significant proportion of patients, the disease course is accompanied by pronounced systemic inflammatory response and hemostasis changes. This is associated with a high risk of complications, especially in patients with concomitant cardiovascular pathology. The aim of the study was to analyze and systematize the literature data on the pathogenesis, clinical course, and outcomes of myocardial infarction (MI) in patients with COVID-19. For review, publications indexed in the PubMed, Google Scholar, Web of Science, and Cyberleninka databases were used. The search depth was 2 years, starting from 2020. The review is based on summarized data from the most relevant clinical studies, reports and systematic reviews. The literature analysis made it possible to conclude that the published data on MI in patients with COVID-19 are currently contradictory. Multiple thrombosis, sepsis, macrophage activation, increasing hypoxemia, imbalance between myocardial oxygen supply and demand in patients with severe COVID-19 have led to a high incidence of type 1 and type 2 MI. It should be especially noted that in a number of cases, MI with COVID-19 occurs in patients with intact coronary arteries, and its course is associated with a high incidence of complications, which, in turn, leads to a significant increase in short- and mid-term mortality.

Fluid–structure interaction (FSI) simulation for studying the impact of atherosclerosis on hemodynamics, arterial tissue remodeling, and initiation risk of intracranial aneurysms

The biomechanical and hemodynamic effects of atherosclerosis on the initiation of intracranial aneurysms (IA) are not yet clearly discovered. Also, studies for the observation of hemodynamic variation due to atherosclerotic stenosis and its impact on arterial remodeling and aneurysm genesis remain a controversial field of vascular engineering. The majority of studies performed are relevant to computational fluid dynamic (CFD) simulations. CFD studies are limited in consideration of blood and arterial tissue interactions. In this work, the interaction of the blood and vessel tissue because of atherosclerotic occlusions is studied by developing a fluid and structure interaction (FSI) analysis for the first time. The FSI presents a semi-realistic simulation environment to observe how the blood and vessels' structural interactions can increase the accuracy of the biomechanical study results. In the first step, many different intracranial vessels are modeled for an investigation of the biomechanical and hemodynamic effects of atherosclerosis in arterial tissue remodeling. Three physiological conditions of an intact artery, the artery with intracranial atherosclerosis (ICAS), and an atherosclerotic aneurysm (ACA) are employed in the models with required assumptions. Finally, the obtained outputs are studied with comparative and statistical analyses according to the intact model in a normal physiological condition. The results show that existing occlusions in the cross-sectional area of the arteries play a determinative role in changing the hemodynamic behavior of the arterial segments. The undesirable variations in blood velocity and pressure throughout the vessels increase the risk of arterial tissue remodeling and aneurysm formation.

Effect of selective dopamine D3 and D4 receptor agonists on trunk pulmonary artery vascular reactivity from control and monocrotaline-treated rats.

Dopamine D1-like and D2-like receptors are expressed in the pulmonary arteries, however there is a little information about their effect on vascular tone in pulmonary circulation, even the vascular effect of activation of the dopamine D3 and D4 subtypes in physiological and pathological conditions such as pulmonary hypertension is unknown. The objective of this study was to evaluate the vascular response of trunk pulmonary artery rings from saline and monocrotaline-treated rats in the presence of selective dopamine receptor agonists. In trunk pulmonary artery rings with intact and denuded endothelium, cumulative concentration-response curves were performed for phenylephrine, acetylcholine, and dopamine receptor agonists (apomorphine-D2-like, SKF38393-D1, quinpirole-D2/D3, 7-OH-DPATD3, and PD168077-D4) alone and in the presence of corresponding selective dopamine receptor antagonists (SCH23390-D1, raclopride-D2/D3, U99194 maleate-D3, and L-745,870-D4). Contractile and relaxant effects generated during the activation with phenylephrine and acetylcholine, respectively, were significantly reduced in intact and denuded endothelium trunk pulmonary artery rings from monocrotaline rats in comparison with control rats. All dopamine receptor agonists, except the 7-OH-DPAT, produced significant vascular relaxation in intact trunk pulmonary artery rings precontracted with phenylephrine in both experimental groups. Also, the vascular relaxation of SKF38393, and particularly apomorphine and PD168077 was significant in denuded endothelium trunk pulmonary artery rings from control and monocrotaline groups. Furthermore, the vasorelaxation induced by these dopamine agonists was significantly reduced in pulmonary preparations from monocrotaline-treated rats in comparison to that recorded in preparations from control rats. The effect of dopamine receptor agonists decreased significantly in the presence of the corresponding antagonist in both experimental groups. The results support that dopamine D4 receptor agonist induces significant vascular relaxation, whereas dopamine D3 receptor agonist induces vasoconstriction in intact and denuded endothelium trunk pulmonary artery rings in control and monocrotaline-induced pulmonary arterial hypertension rats.

Endothelial signalling operates on a small‐world network to control vascular function

The endothelium is the innermost layer of all blood vessels and it controls a host of cardiovascular functions including vascular contractility, hemostasis, inflammation and the exchange of nutrients and waste products between circulating blood and tissue. The importance of the endothelium is clear since changes in the behaviour of this single layer of cells underlies almost all cardiovascular disease. To control each cardiovascular function, the endothelium processes and responds to endless streams of information that originate from multiple sources (i.e. blood cells, hormones, neighboring endothelial cells or underlying smooth muscle cells). To process so much information, the endothelium utilises distributed sensing on spatially‐distinct populations of cells that are primed to detect specific activators. These spatially‐distinct populations communicate across the endothelial network to coordinate vascular responses. The nature of the endothelial network, and how communication is achieved, is currently not understood. Here, by examining the Ca2+ responses in thousands of endothelial cells in intact arteries, we show how the endothelial network operates.Network organization controls overall system behaviour by determining the signal propagation speed, the robustness of the system to failures and attack, and the degree of synchronizability in the system. To determine the endothelial network structure, we used network (graph) theory. Graph theory has gained much attention due to its ability to quantify social, technological and biological systems, especially the connectivity and synchronisation of the nervous system. However, no studies have examined the network structure employed by the endothelium in the control of cardiovascular function. We analysed muscarinic‐ and histaminergic‐evoked Ca2+ activity from ~1000 endothelial cells from intact resistance arteries. Ca2+ signals were separately analysed in each of the 1000 individual endothelial cells using a custom‐written Python algorithm.Ca2+ activity in active cells was cross‐correlated and compared to a stochastic model to statistically quantify network connections. We show highly‐correlated Ca2+ activities occurred in multiple, separate, cell clusters for each agonist. The network communication links between the clusters exhibited unexpectedly short path‐lengths, i.e. the number of links between active cells was significantly shorter than expected when active cells were randomly positioned. The number of connections between active cells (degree distribution) followed a power‐law relationship, revealing a scale‐free network topology. The path‐length and degree distribution reveal an endothelial network with a ‘small‐world’ configuration. The small‐world configuration confers particularly dynamic endothelial properties including high signal‐propagation speed, stability and a high degree of synchronizability.These findings show that endothelial network design is effective for local and global efficiency in the interaction of cells, and for rapid and robust communication to efficiently control cardiovascular activity. The network organization explains how coordinated cell activity occurs across large regions of endothelium, despite sensing being distributed on spatially‐distinct populations of cells.

Mitochondrial oxidative phosphorylation fuels endothelial control of blood vessel tone

Arteries and veins are lined by non‐proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis to fuel each of these energy‐demanding processes. However, endothelial metabolism has mainly been studied in the context of proliferative cells in angiogenesis, and little is known about energy production in endothelial cells within the fully‐formed vascular wall.Using intact arteries isolated from rats and mice, we show that inhibiting mitochondrial oxidative phosphorylation at mitochondrial complex V disrupts calcium‐dependent, nitric oxide‐mediated endothelial cell control of vascular tone. Basal, mechanically‐activated, and agonist‐evoked calcium activity in intact artery endothelial cells are each prevented by inhibiting mitochondrial ATP synthesis. This effect is mimicked by blocking the transport of pyruvate, the master fuel for mitochondrial energy production, through the mitochondrial pyruvate carrier. The role for endothelial cell energy production is independent of species, sex, or vascular bed.These data show that mitochondrial ATP is necessary for the obligatory role of endothelial cells in the control of blood vessel diameter, and validate the idea of targeting endothelial cell metabolism to treat endothelial cell dysfunction in cardiovascular disease.

4D diSPIM Myography Reveals Changes in Endothelial Cell Shape and Ca2+ Signaling in Response to Intravascular Pressure in ex vivo Resistance‐sized Arteries

The vascular endothelium is critical in promoting vasodilation of resistance‐sized arteries through Ca2+dependent pathways. The endothelium is exposed to mechanical stimulation through changing intravascular pressure and flow. Understanding how the endothelium integrates this information into a change in vascular function requires the ability to simultaneously measure changes vessel diameter and EC Ca2+ signaling with high spatial and temporal resolution. We hypothesized that endothelial cell shape and Ca2+ signaling is pressure dependent. To test this, we combined 4D Dual Inverted Selective Plane of Illumination Microscopy (diSPIM; 3i, CO) with pressure myography. This system allows for imaging of three‐dimensional tissue preparations over time with very low photobleaching and phototoxicity, millisecond temporal resolution, and isometric 320 nm spatial resolution over a large imaging volume (330 x 330 x 150 mm). We designed and fabricated pressure myography chambers that position ex vivo pressurized arteries in the correct orientation for acquisition of high‐resolution fluorescent data via diSPIM while using an inverted microscope base to continuously capture vessel diameter measurements via transmitted IR light. Resistance‐sized mesenteric arteries from mice expressing an endothelium specific GECI are positioned between the diSPIM objectives and maintained at physiologic temperature and pH. We captured fluorescent images of whole pressurized arteries at 80, 60, 40, and 20 mmHg before and after the generation of myogenic tone and in the absence of extracellular Ca2+. As static intravascular pressure is increased, ECs increase in width and decrease in thickness. Myogenic tone minimizes changes in EC shape with changing pressure, however increasing static intravascular pressure decreases local EC Ca2+ signaling. The data demonstrate a relationship between intravascular pressure and EC shape and Ca2+ signaling in intact resistance arteries. This technique provides a method of studying the effects of physiologically relevant mechanical stimuli and the roles of various mechanosensitive mechanisms on vascular function.

Pressure Modulation of Vascular L‐type Calcium Channels: implications to the Myogenic Response

L‐type Ca2+ channels govern smooth muscle [Ca2+] and myogenic tone development through mechanisms traditionally tied to voltage control. While essential, questions remain as to whether voltage is the sole regulatory influence or whether L‐type Ca2+ channels are additionally mechanosensitive. In this context, this study defined whether and by what mechanisms pressure stimuli modulate L‐type Ca2+ channels in rodent (rat &amp; mouse) resistance arteries. Experiments extended from single smooth muscle cells (whole‐cell/single‐channel patch clamp; immunohistochemistry; proximity ligation assay) to intact arteries (pressure myography). Whole‐cell patch clamp electrophysiology revealed that pressure stimuli increased the L‐type Ca2+ current, a phenomenon that single channel analysis attributed to enhanced functional coupling. Subsequent work noted that pressure‐enhanced functional coupling is tied to: 1) PKC‐mediated cooperative gating; and 2) subunit trafficking to caveolae. Functional experiments, using 30 mM KCl to elicit a set depolarization (~‐40 mV), revealed that tone and cytosolic [Ca2+] responses were more pronounced in arteries pressurized to 80 rather than 20 mmHg. These functional results are in alignment with patch clamp observations and suggest that L‐type Ca2+ channels are indeed mechanosensitive. Cumulatively, our results suggest that there is more to L‐type Ca2+ channel regulation than voltage and that pressure sensitivity must be carefully weighed in the healthy and diseased setting. Work continues to precisely define the pressure‐sensitive signaling complexes within vascular smooth muscle.

Impact of MMP-9 Genetic Polymorphism and Concentration on the Development of Coronary Artery Disease in Ukrainian Population.

Coronary artery disease (CAD) is one of the leading causes of death in Europe. It is known that atherosclerosis is the primary risk factor of CAD development. MMP-9 is involved in all stages of atherosclerosis and thus may contribute to CAD emergence. To investigate the influence of MMP-9 on the (CAD) development 25 patients with intact coronary arteries (CA), 40 patients with acute coronary syndrome (ACS), and 63 patients with chronic coronary syndrome (CCS) were enrolled in the study. Real-time PCR was carried out for genotyping on the rs17567-polymorphic locus, and ELISA study was performed to measure the MMP-9 plasma concentration. It was found the lower risk of MI occurrence for AG-carriers (Pa=0.023; ORa = 0.299, 95% CI = 0.106–0.848) in Ukrainian population.

Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Lacrimal Gland Adenoid Cystic Carcinoma: A Long-Term Follow-up Study of a Trimodal Strategy

To report the therapeutic efficacy of integrating neoadjuvant chemotherapy with conventional bimodal therapies for lacrimal gland adenoid cystic carcinoma by providing an additional 8 years of follow-up data on the same cohort of patients whose cumulative 10-year disease-free survival outcomes were reported in 2013. Non-randomized, retrospective, interventional case series. Nineteen consecutive patients treated with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC), orbital exenteration, chemoradiotherapy, and adjuvant intravenous chemotherapy at a single institution were included. Analyses were undertaken of locoregional recurrences and distant metastases, disease-free survival time, TNM tumor stage at presentation, response to IACC, and prognostic impact of positive resection margins. The main outcome measures were overall survival, disease-free survival, disease relapse, positive tumor resection margins, and tumor stage at presentation. Eight patients with an intact lacrimal artery (group 1), 7 with AJCC stage T4a-c, had significantly better overall survival (87.5% versus 14.3% at 15 years), disease-specific mortality, and recurrences (all < .001, log-rank test) than prior conventionally treated patients from the Bascom Palmer Eye Institute. Group 1 was superior to group 2, patients lacking an intact lacrimal artery, concerning overall survival (P=.042) and recurrence (P=.017), but with no significant difference in disease-specific mortality (P=.23). Group 2 was associated with a significantly lower cause-specific mortality than the institutional comparator group (P=.039). Prior tumor resection with lateral wall osteotomy and failure to adhere to all protocol elements were adverse prognostic factors for suboptimal outcomes. Positive tumor margins increased the risk of all-cause mortality 4.1 times (P=.036, stratified Cox proportional hazards regression) and disease-specific mortality 8.0 times (P=.043, stratified Cox proportional hazards regression) than a patient with negative margins. Extended follow-up supplemented with AJCC staging data supports neoadjuvant IACC as an integral component of a trimodal treatment strategy in patients with an intact lacrimal artery. Protocol elements implemented as designed appear to have improved overall survival and decreased disease relapse in this cohort. This extended long-term IACC dataset suggests that a critical bar of at least 15 years of follow-up is appropriate for assessing the efficacy of current conventional and future globe-sparing bimodal therapies.

The art of tackling strabismus skillfully by sparing vessels.

Background:Detaching a rectus muscle irreparably destroys its ciliary artery circulation which also supplies the anterior segment of the eye.Purpose:To educate strabismus surgeons about a method of detaching a muscle without compromising anterior segment circulation.Synopsis:A limbal based conjunctival incision is made. The muscle is identified, separated from its attachments and secured with 6-0 Vicryl. The anterior ciliary vessel supplying it is isolated by making a small snip incision in the muscle capsule with delicate blunt dissection parallel to the anterior ciliary artery The muscle is detached from its original insertion. The muscle is tied to sclera at the intended point of recession. The intact anterior ciliary artery, thus will continue to function, untouched.Highlights:We recommend pre-placing the sutures in the muscle and also in the sclera at the point of reattachment to avoid possible stretching and breaking of anterior ciliary vessels at the time of muscle detachment and also to dissect the artery free from muscle several millimeters more than the intended recession in order to spare the anterior ciliary circulation in strabismus surgery.Video link: https://youtu.be/Bn050Ihu9rU

Restricted Intimal Ca2+ Signaling Associated With Cardiovascular Disease.

Endothelial dysfunction is a key feature of cardiovascular disease (CVD) including atherosclerosis. Impaired endothelial signaling leads to plaque formation, vascular wall remodeling and widespread cardiovascular dysregulation. The specific changes along the vascular intima associated with atherosclerosis, including the vulnerable circulation downstream of the flow obstruction, remain poorly understood. Previous findings from animal models suggest that preservation of a distinct Ca2+ signaling profile along the arterial endothelial network is crucial for maintaining vasculature homeostasis and preventing arterial disease. Ca2+ signaling in the intact human artery intima has not been well characterized. Here, we employed confocal imaging and a custom analysis algorithm to assess the spatially and temporally dynamic Ca2+ signaling profiles of human peripheral arteries isolated from the amputated legs of patients with advanced CVD (peripheral artery disease and/or diabetes) or patients who had lost limbs due to non-cardiovascular trauma. In all tibial artery branches (0.5–5 mm diameter) assessed, the intima consistently elicited a broad range of basal Ca2+ signals ranging from isolated focal transients to broad waves. Arteries from patients with existing CVD displayed a restricted intimal Ca2+ signaling pattern characterized by diminished event amplitude and area. Stimulation of type-4 vanilloid transient receptor potential channels (TRPV4) amplified endothelial Ca2+ signals; however, these signals remained smaller and spatially confined in arteries from patients with CVD verses those without CVD. Our findings reveal a characteristic underlying basal Ca2+ signaling pattern within the intima of human peripheral arteries and suggest a distinct truncation of the inherent Ca2+ profile with CVD.

Spatially resolved transcriptomics for evaluation of intracranial vessels in a rabbit model: Proof of concept.

Better understanding of vessel biology and vascular pathophysiology is needed to improve understanding of cerebrovascular disorders. Tissue from diseased vessels can offer the best data. Rabbit models can be effective for studying intracranial vessels, filling gaps resulting from difficulties acquiring human tissue. Spatially-resolved transcriptomics (SRT) in particular hold promise for studying such models as they build on RNA sequencing methods, augmenting such data with histopathology. Rabbit brains with intact arteries were flash frozen, cryosectioned, and stained with H&E to confirm adequate inclusion of intracranial vessels before proceeding with tissue optimization and gene expression analysis using the Visium SRT platform. SRT results were analyzed with k-means clustering analysis, and differential gene expression was examined, comparing arteries to veins. Cryosections were successfully mounted on Visium proprietary slides. Quality control thresholds were met. Optimum permeabilization was determined to be 24 min for the tissue optimization step. In analysis of SRT data, k-means clustering distinguished vascular tissue from parenchyma. When comparing gene expression traits, the most differentially expressed genes were those found in smooth muscle cells. These genes were more commonly expressed in arteries compared to veins. Intracranial vessels from model rabbits can be processed and analyzed with the Visium SRT platform. Face validity is found in the ability of SRT data to distinguish vessels from parenchymal tissue and differential expression analysis accurately distinguishing arteries from veins. SRT should be considered for future animal model investigations into cerebrovascular diseases.

Acute coronary syndrome in patients under 35 years old

Objective. To evaluate the clinical and demographic characteristics of a group of patients under 35 years old admitted with acute coronary syndrome, as well as the features of coronary bed damage and endovascular treatment.Material and methods. A retrospective analysis of the group of patients aged 30 to 35, admitted to the Regional Vascular Center with a diagnosis of acute coronary syndrome in the period from 2019 to June 2021, was carried out. The study included 72 patients with ACS, regardless of the ST segment changes on the electrocardiogram, were admitted to the hospital by the emergency medical service referral. Positive troponins were detected in all the patients by qualitative analysis. Upon admission, they were sent to a catheterization laboratory. An examination was carried out according to the recommendations of medical care, as well as selective coronary angiography and, if indicated, stenting of the coronary arteries was performed.Results. When analyzing the clinical and demographic characteristics of the group, attention has been drawn to the absolute predominance of males — 71 (98.7%), urban residents — 64 (88.9%), low frequency of bad habits: tobacco smoking in 13 (18.1%) and alcohol abuse in 2 (2.8%) patients, the absence of concomitant pathology, a signifi cant time from the onset of symptoms to calling an ambulance (165 [90; 263]). According to the results of angiography, it should be noted the possibility of acute coronary syndrome with intact coronary arteries is 9 (27.3%) among all ACS cases with ST segment elevation and 29 (74.3%) with ACS without ST segment elevation, while in one third of the above episodes (13 (34.2%)) ACS was caused by the presence of a muscle “bridge” in the basin of the anterior descending artery, a concomitant phenomenon of slowed blood fl ow. The attention has been also drawn to the almost equal proportions of acute thrombotic occlusion (19 (55.9%)) and haemodynamically signifi cant hemadostenosis (14 (41.2%)) as the cause of ACS.Conclusion. In patients under 35 years old with a typical clinical. picture, positive troponins, with a qualitative analysis, there is a high probability of pathological changes in the coronary bed, regardless of the ST segment changes, which requires X-ray endovascular methods of diagnosis and treatment. Angiographic features of the coronary artery lesion in young people are the discreteness of the lesion in the proximal or middle sections of the arteries, the high frequency of thrombotic occlusions, the predominant lesion of the anterior descending or right coronary arteries, the low frequency of calcifi cation of the coronary arteries.

ASSOCIATION OF MMP-9 GENETIC POLYMORPHISM AND ММР-9 CONCENTRATION WITH ECHOCARDIOGRAPHIC PARAMETERS IN UKRAINIAN PATIENTS WITH CORONARY ARTERY DISEASE

Introduction. Cardiovascular diseases are the main cause of reduced life expectancy, workability, and death among the people of Eastern Europe. Matrix metalloproteinase-9 (MMP-9) is known as one of the leading factors involved in the development and progression of atherosclerosis and heart remodeling. The increasing sizes of the heart’s chambers lead to changes in the electrophysiological properties of the myocardium and to the subsequent occurrence of arrhythmias and conduction disorders. Materials and methods. The study included 25 patients with intact coronary arteries (CA), 40 patients with acute coronary syndrome (ACS) and 63 patients with chronic coronary syndrome (CCS) to investigate the effect of MMP-9 polymorphism and its serum concentration on changes in echocardiographic parameters. Real-time PCR was carried out for genotyping on the rs17567-polymorphic locus and ELISA study was performed to measure the MMP-9 plasma concentration. Results. Statistically significant differences were found in the thickness of the posterior wall of the heart among carriers of the G-allele and AA-homozygotes for the MMP-9 rs17576-single nucleotide polymorphism but only in patients with ACS. The size of the left ventricle posterior wall can be predicted for carriers of these genotypes. Conclusions. The study revealed no statistically significant relationship between MMP-9 concentration and echocardiographic parameters in patients with ACS and CCS. However, there were statistically significant differences in the left atrium diameter and thickness of the posterior wall of the left ventricle depending on the genotype for MMP-9 rs17576-single nucleotide polymorphism only in patients with ACS. The size of the posterior wall of the left ventricle can be predicted for carriers of AG and GG genotypes.

Computer modeling of the area of carotid endarterectomy with patches of various forms

To describe geometric models of carotid artery bifurcation and computer modeling of carotid endarterectomy (CEA) with patches of various configurations. The method was demonstrated on a reconstructed model of intact vessel based on preoperative CT of the affected vessel in a certain patient. Blood flow is modeled by computational fluid dynamics using Doppler ultrasound data. Risk factors were assessed considering hemodynamic parameters of vascular wall associated with WSS. We studied hemodynamic results of 10 virtual CEA with patches of various shapes on the example of a reconstructed intact artery in a particular patient. Patch implantation is aimed at prevention of carotid artery narrowing since simple suture without a patch can reduce circumference of the artery by 4-5 mm. This result adversely affects blood flow. On the other hand, too wide a patch creates aneurysm-like deformation of internal carotid artery bulb. It is not optimal due to a large recirculation zone. It was found that patch width approximately equal to 3 mm ensures an optimal hemodynamic result. Deviations from this median value, both upward and downward, impair hemodynamics while the absence of a patch results the worst result. The proposed computer modeling technique is able to provide a personalized patch selection for CEA with low risk of restenosis in long-term follow-up period.

Assessment of the role of IL6 and IL10 gene polymorphisms as a risk factor for the development of restenosis in patients after implantation of drug-eluting stents

Relevance. Currently, the number of percutaneous coronary interventions continues to increase, which leads to an increase in the absolute number of restenosis cases, which is the main complication of the long-term postoperative period. The search for risk factors responsible for restenosis and artery re-narrowing mechanisms in order to prevent this complication is an important goal in interventional cardiology. Risk factors for the restenosis development include clinical, angiographic and genetic factors. An active search for biomolecular markers associated with the coronary artery restenosis is currently underway. Objective: to study the role of polymorphic variants C-174G of the IL6 gene and C-819T of the IL10 gene as a risk factor for the development of restenosis in patients after stent implantation. Materials and Methods : The study included 113 patients with stable coronary artery disease, who had previously undergone balloon angioplasty and implantation of drug-eluting stents, and 62 patients with intact arteries that were included to the control group. Statistical data processing was carried out using the R-language program and the SPSS Statistics 20 software package. Results: GG genotype for IL6 gene was associated with the development of coronary artery disease. In the subgroup of patients over 65 years of age and instent restenosis, the GG genotype was significantly less frequent. The homozygous CC genotype for IL10 gene was associated with rapid angiographic in-stent restenosis progression.

“A STUDY OF ATHEROSCLEROSIS OF RIGHT CORONARY ARTERY AND THORACIC AORTA IN POST MORTEM CASES”

Background: Atherosclerosis is a chronic disease which primarily affects the intima of large and medium sized muscular arteries, commonly involving aorta, coronary arteries and cerebral arteries. The contribution of atherosclerosis in morbidity and mortality of young adults is on the rise. Objective: To demonstrate histopathological spectrum of atherosclerotic lesions in Right Coronary Artery and Thoracic aorta and to compare the age, gender and BMI variation in prevalence of atherosclerotic lesions. 150 specime Materials And Methods: ns of heart with intact coronary arteries and thoracic aorta received by Department of pathology, Shimoga Institute of Medical Sciences, Shivamogga. Heart was grossly examined and sections were taken from Right Coronary Artery and Thoracic Aorta which were processed and stained with Haematoxylin and Eosin. Microscopically typing of the atherosclerotic lesion was made using American Heart Association classication of atherosclerosis. Of the Results: 150 cases, males 91% and females 9% were affected. Majority of the cases were in the age group of 30-40 years (33.33%) and BMI range of 18.6- 24.9 (72.67%). Commonest type of atherosclerosis in Right coronary artery was type 5 (Fibroatheroma) (25.33%) and in Thoracic aorta was type 3 (Preatheroma) (30%). Grade 1 Luminal narrowing (1-25% obstruction) was most commonly seen in Right coronary Artery (50% cases). Conclusion: Due to increase in cardiac death rates screening of cardiovascular risk factors, preventive measures, life style modication and having healthy dietary habits should be implemented early in 3rd decades of young Indians to retard the progression of atherosclerosis.

Modified Le Fort II approach with adequate vascularization preservation in midface allotransplantation: Mock surgery

IntroductionIt is critical to preserve adequate vascularization in midface allotransplantation, the major complication of which is inadequate blood supply in palate area supplying mainly by internal maxillary artery. Therefore, the aim of this study is to explore a modified Le Fort II approach entailing midface vascularization enhancement. Materials and methodsTen cadaveric heads were used in mock surgery. A conventional approach was used on seven cadaveric heads to harvest external carotid artery-facial artery-internal maxillary artery axis. On the remaining three cadaveric heads, modified Le Fort II approach was applied where the internal maxillary artery was harvested after cutting off zygomatic arches and rami of the mandible. ResultsThe conventional approach had difficulty harvesting internal maxillary artery, which left the facial artery the only blood supply to midface. Modified Le Fort II approach with Computerized surgical planning (CSP) assisted, on the other hand, could completely unveil and harvest intact internal maxillary artery after osteotomy of mandibular ramus. ConclusionThe modified Le Fort II approach with CSP and ultrasonic bone cutter assisted can maximally preserve internal maxillary system with ease. This approach optimizes midface allotransplantation in clinical practice in future.