Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.

Background: Citrullination represents a post-translational modification primarily mediated by peptidylarginine deiminase (PADI) 2 and 4 and resulting in the conversion of positively charged peptidylarginine to neutrally charged peptidylcitrulline. Molecular consequences of citrullination include the generation of neoepitopes which provoke the production of autoantibodies implicated in the development of autoimmune diseases. As citrullination initiates, promotes, and is enhanced by aseptic inflammation which plays a pivotal role in atherosclerosis, we proposed that citrullination might accompany the development of atherosclerotic vascular disease.

Anti-Inflammatory Effect of Atorvastatin on Primary Human Endothelial Cells Incubated under Genotoxic Load.

The level of cytokine expression was measured in human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells exposed to 500 ng/ml alkylating mutagen mitomycin C (MMC) and 5 μM atorvastatin. It was found that treatment of MMC-exposed HCAEC with atorvastatin decreased secretion of macrophage migration inhibitory factor (MIF), IL-8, and IL8 gene expression, but increased the expression of SERPINE1 gene encoding the PAI-1 protein. In atorvastatin-treated HITAEC, the concentration of MIF protein and the expression of the IL8 and SERPINE1 genes were reduced.

Inflammatory Response Genes' Polymorphism Associated with Risk of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients.

The cytokine response of human coronary artery endothelial cells treated with doxorubicin: results of an in vitro experiment.

The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 μg/ml and 6 μg/ml) was evaluated using enzyme-linked immunosorbent assay and qPCR. Cultivation of cells in the presence of these concentrations of doxorubicin for 24 h, upregulated expression of the following genes: IL6 (by 2.30 and 2.

Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction.

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction.

Calciprotein Particles Induce Cellular Compartment-Specific Proteome Alterations in Human Arterial Endothelial Cells.

Calciprotein particles (CPPs) are indispensable scavengers of excessive Ca and PO ions in blood, being internalised and recycled by liver and spleen macrophages, monocytes, and endothelial cells (ECs). Here, we performed a pathway enrichment analysis of cellular compartment-specific proteomes in primary human coronary artery ECs (HCAEC) and human internal thoracic artery ECs (HITAEC) treated with primary (amorphous) or secondary (crystalline) CPPs (CPP-P and CPPs, respectively). Exposure to CPP-P and CPP-S induced notable upregulation of: (1) cytokine- and chemokine-mediated signaling, Ca-dependent events, and apoptosis in cytosolic and nuclear proteomes; (2) H and Ca transmembrane transport, generation of reactive oxygen species, mitochondrial outer membrane permeabilisation, and intrinsic apoptosis in the mitochondrial proteome; (3) oxidative, calcium, and endoplasmic reticulum (ER) stress, unfolded protein binding, and apoptosis in the ER proteome.

The Role of Insulin Resistance in the Development of Complications after Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease.

Unlabelled: The aim of the study was to investigate the effect of carbohydrate metabolism disorders and insulin resistance indices on the immediate results of coronary artery bypass grafting (CABG).

Method: Patients with coronary artery disease who underwent CABG ( = 383) were examined to determine glycemic status, free fatty acid and fasting insulin levels, and insulin resistance indices (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), McAuley index, Quantitative Insulin Sensitivity Check Index (QUICKI), Revised-QUICKI). Patients were assessed for the development of perioperative complications and their length of stay in the hospital.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity.

Major adverse cardiovascular events occurring upon coronary artery bypass graft surgery are typically accompanied by endothelial dysfunction. Total arterial revascularisation, which employs both left and right internal thoracic arteries instead of the saphenous vein to create a bypass, is associated with better mid- and long-term outcomes. We suggested that molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs) are coherent in terms of transcriptomic and proteomic signatures, which were then investigated by RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively.

The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease.

Coronary artery disease (CAD) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. The maintenance of endothelial homeostasis and vitamin D metabolism play an important role in CAD pathogenesis. This study aimed to determine the association of endothelial homeostasis and vitamin D metabolism gene polymorphism with CAD severity.

Comparison of the Patency and Regenerative Potential of Biodegradable Vascular Prostheses of Different Polymer Compositions in an Ovine Model.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility.

TREM-1 as a Marker of Multiple Organ Failure in Cardiac Surgery.

Systemic inflammatory response syndrome (SIRS) frequently accompanies early postoperative period after cardiac surgery and in some cases is complicated by multiple organ failure (MOF). Inherited variation in the innate immune response genes (e.g.

Atorvastatin Can Modulate DNA Damage Repair in Endothelial Cells Exposed to Mitomycin C.

HMG-CoA reductase inhibitors (statins) are widely used in the therapy of atherosclerosis and have a number of pleiotropic effects, including DNA repair regulation. We studied the cytogenetic damage and the expression of DNA repair genes (, , and ) in human coronary artery (HCAEC) and internal thoracic artery endothelial cells (HITAEC) in vitro exposed to mitomycin C (MMC) (positive control), MMC and atorvastatin (MMC+Atv), MMC followed by atorvastatin treatment (MMC/Atv) and 0.9% NaCl (negative control).

Refraining from Packed Red Blood Cells in Cardiopulmonary Bypass Priming as a Method of Neuroprotection in Pediatric Cardiac Surgery.

Unlabelled: Congenital heart defect (CHD) surgeries are performed with cardiopulmonary bypass (CPB) and are complicated by several factors that affect the child's brain. However, to date, the number of studies on brain protection in cardiac surgery remains small. The aim of this study was to assess the impact of refraining from using packed red blood cells (PRBCs) in priming solutions in children with congenital defects (CHDs) who require surgical interventions using CPB to prevent brain injury in the postoperative period.

Calciprotein Particles Cause Physiologically Significant Pro-Inflammatory Response in Endothelial Cells and Systemic Circulation.

Calciprotein particles (CPPs) represent an inherent mineral buffering system responsible for the scavenging of excessive Ca and PO ions in order to prevent extraskeletal calcification, although contributing to the development of endothelial dysfunction during the circulation in the bloodstream. Here, we performed label-free proteomic profiling to identify the functional consequences of CPP internalisation by endothelial cells (ECs) and found molecular signatures of significant disturbances in mitochondrial and lysosomal physiology, including oxidative stress, vacuolar acidification, accelerated proteolysis, Ca cytosolic elevation, and mitochondrial outer membrane permeabilisation. Incubation of intact ECs with conditioned medium from CPP-treated ECs caused their pro-inflammatory activation manifested by vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) upregulation and elevated release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1/ C-C motif ligand 2 (MCP-1/CCL2).

Mitochondrial DNA as a Candidate Marker of Multiple Organ Failure after Cardiac Surgery.

Assess the level of mitochondrial DNA depending on the presence of multiple organ failure in patients after heart surgery. The study included 60 patients who underwent surgical treatment of valvular heart disease using cardiopulmonary bypass. Uncomplicated patients were included in the 1st group ( = 30), patients with complications and multiple organ failure (MOF) were included in the 2nd group ( = 30).

[Genotoxic stress leads to the proinflammatory response of endothelial cells: an in vitro study].

It was shown, that genotoxic stress can trigger endothelial disfunction and atherosclerosis, but the molecular genetic mechanisms of this process are poorly investigated. At the same time, inflammation also plays the important role in atherogenesis. This study aimed access of inflammatory marker expression in the endothelial cells exposed to alkylating mutagen mitomycin C (MMC).

Identification of Key Genes and Pathways in Genotoxic Stress Induced Endothelial Dysfunction: Results of Whole Transcriptome Sequencing.

Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide. Endothelial disfunction underlying the atherogenesis can be triggered by genotoxic stress in endothelial cells. In the presented research whole transcriptome sequencing (RNA-seq) of human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells in vitro exposed to 500 ng/mL mitomycin C (treatment group) or 0.

Endothelial Dysfunction in the Context of Blood-Brain Barrier Modeling.

Here, we discuss pathophysiological approaches to the defining of endothelial dysfunction criteria (i.e., endothelial activation, impaired endothelial mechanotransduction, endothelial-to-mesenchymal transition, reduced nitric oxide release, compromised endothelial integrity, and loss of anti-thrombogenic properties) in different in vitro and in vivo models.

Early Postoperative Immunothrombosis of Bioprosthetic Mitral Valve and Left Atrium: A Case Report.

A 72-year-old female patient with mixed rheumatic mitral valve disease and persistent atrial fibrillation underwent mitral valve replacement and suffered from a combined thrombosis of the bioprosthetic valve and the left atrium as soon as 2 days post operation. The patient immediately underwent repeated valve replacement and left atrial thrombectomy. Yet, four days later the patient died due to the recurrent prosthetic valve and left atrial thrombosis which both resulted in an extremely low cardiac output.

[Transcription of DNA-Methyltransferases in Endothelial Cells Exposed to Mitomycin C].

DNA-methyltransferases catalyze DNA methylation in the CpG sites, which play an important role in the maintenance of genome stability. The association between DNA methylation and genotoxic stress resulting in the action of various clastogens has been shown. Genotoxic stress is one of the triggers of endothelial dysfunction.