Aim: This study was undertaken to investigate the physicochemical properties of modified low density lipoprotein (LDL) in diabetes.

Methods: LDL from 10 type 1 and 10 type 2 diabetic patients, as well as LDL from 10 non-diabetic subjects, was subdivided into bound and non-bound fractions by affinity chromatography on Ricinus communis agglutinin-agarose, and further characterized by sialic acid content, hydrated density, electrophoretic mobility, and the ability to induce cholesterol deposition in cultured cells.

Results: The non-bound LDL fraction was similar to native LDL from healthy subjects, with respect to its physicochemical properties, and did not produce intracellular cholesterol accumulation. The bound LDL fraction was characterized by several alterations differentiating it from non-bound LDL, namely, significantly lowered sialic acid content (by 35-50%, compared with non-bound LDL), increased electrophoretic mobility (by 40-50%), increased hydrated density (difference in modae, 5.6-5.9 mg/mL), and smaller particle size (difference in modae, 3.8-4.9 nm). Bound LDL possessed the ability to induce a 2.1- to 2.7-fold increase in intracellular cholesterol content.

Conclusion: The results showed the presence of a dense, small, more electronegative, desialylated LDL subfraction in the blood of diabetic patients, which is in vivo modified atherogenic LDL.

Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles.

Aim: This paper aims to compare the mechanical performance of metallic (Xience) and bioresorbable polymeric (Elixir) stents during the process of crimping and deployment.

Methods: Finite element software ABAQUS was used to create the geometrical models and meshes for the balloon, stent and diseased artery. To simulate the crimping of stents, 12 rigid plates were generated around the stent and subjected to radially enforced displacement. The deployment of both stents was simulated by applying internal pressure to the balloon, where hard contacts were defined between balloon, stent and diseased artery.

Results: Elixir stent exhibited a lower expansion rate than Xience stent during deployment. The stent diameter achieved after balloon deflation was found smaller for Elixir stent due to higher recoiling. Lower level of stresses was found in the plaque and artery when expanded by Elixir stent. Reduced expansion, increased dogboning and decreased vessel stresses were obtained when considering the crimping-generated residual stresses in the simulations.

Conclusion: There is a challenge for polymeric stents to match the mechanical performance of metallic stents. However, polymeric stents impose lower stresses to the artery system due to less property mismatch between polymers and arterial tissues, which could be clinically beneficial.

Epsins, endocytic adaptor proteins required for internalization of ubiquitylated receptors, are generally upregulated in human cancers. It has been characterized that mice deficient of epsins in the endothelium inhibit tumor growth by dysregulating vascular endothelial growth factor receptor-2 (VEGFR2) signaling and non-productive tumor angiogenesis. Binding of the epsin ubiquitin (Ub)-interacting motif (UIM) with ubiquitylated VEGFR2 is a critical mechanism for epsin-dependent VEGFR2 endocytosis and degradation, indicative of epsin UIM as a potential therapeutic target. A Computer Assisted Drug Design approach was utilized to create the UIM mimetic peptides for the functional competition of epsin binding sites in ubiquitylated VEGFR2 in vivo. Specifically targeting VEGFR2 in the tumor vasculature, the chemically synthesized chimeric UIM peptide, UPI, causes non-functional tumor angiogenesis, retards tumor growth, and increases survival rates in several tumor models. The authors showed that UPI binds ubiquitylated VEGFR2 to form a supercomplex in an Ub-dependent fashion. Collectively, the UPI targeting strategy offers a potentially novel treatment for cancer patients who are resistant to current anti-angiogenic therapies. In this review, the authors outline the main points of this research specifically as a potential application for glioma tumor therapy.

Extracorporeal blood purification is becoming increasingly important in intensive therapy for multiple organ dysfunction syndrome (MODS) and sepsis, considering all of their pathophysiological aspects. The results of treatment, particularly in children, considering their anatomical and physiological features, are related to the severity and progression of organ failure, the indications that are found, the choice of method, and the timely initiation of blood purification. Multiple organ support therapy is the aim of introducing and applying blood purification today. Various extracorporeal blood purification techniques directly affect the molecular and electrolyte composition of blood and influence all structures of the human body, which can allow us to correct, recover, replace and maintain homeostasis in MODS. The potential of new extracorporeal molecular technologies allows their successful use in severe cardiac and respiratory failure, acute kidney injury and hepatic dysfunction and in complex therapy for severe infections and sepsis and extreme metabolic violations. Adult and pediatric patients after cardiac surgery with cardiopulmonary bypass form a special cohort that often requires the application of various intra- and extracorporeal techniques due to the development of MODS, infections and sepsis in the postoperative period.

Sternal non-union is a rare but serious complication post-sternotomy. It is defined as sternal pain with clicking, instability, or both for more than 6 months in the absence of infection and usually presents in an outpatient setting. It may result in multiple admissions to the hospital for surgical debridement and wound care therapies. Several risk factors have been identified in the literature but treatment options are limited. Proven benefits of increased stability and decreased incidence of non-union using the principles of rigid fixation have been described in other surgical specialties such as orthopaedic surgery. Employing this, the authors describe the first successful sternal non-union fixation using the Titanium Sternal Fixation System (DepuySynthes) in Scotland.

Aim: This paper aims to compare the mechanical performance of metallic (Xience) and bioresorbable polymeric (Elixir) stents during the process of crimping and deployment.

Methods: Finite element software ABAQUS was used to create the geometrical models and meshes for the balloon, stent and diseased artery. To simulate the crimping of stents, 12 rigid plates were generated around the stent and subjected to radially enforced displacement. The deployment of both stents was simulated by applying internal pressure to the balloon, where hard contacts were defined between balloon, stent and diseased artery.

Results: Elixir stent exhibited a lower expansion rate than Xience stent during deployment. The stent diameter achieved after balloon deflation was found smaller for Elixir stent due to higher recoiling. Lower level of stresses was found in the plaque and artery when expanded by Elixir stent. Reduced expansion, increased dogboning and decreased vessel stresses were obtained when considering the crimping-generated residual stresses in the simulations.

Conclusion: There is a challenge for polymeric stents to match the mechanical performance of metallic stents. However, polymeric stents impose lower stresses to the artery system due to less property mismatch between polymers and arterial tissues, which could be clinically beneficial.

Aim: This study was undertaken to investigate the physicochemical properties of modified low density lipoprotein (LDL) in diabetes.

Methods: LDL from 10 type 1 and 10 type 2 diabetic patients, as well as LDL from 10 non-diabetic subjects, was subdivided into bound and non-bound fractions by affinity chromatography on Ricinus communis agglutinin-agarose, and further characterized by sialic acid content, hydrated density, electrophoretic mobility, and the ability to induce cholesterol deposition in cultured cells.

Results: The non-bound LDL fraction was similar to native LDL from healthy subjects, with respect to its physicochemical properties, and did not produce intracellular cholesterol accumulation. The bound LDL fraction was characterized by several alterations differentiating it from non-bound LDL, namely, significantly lowered sialic acid content (by 35-50%, compared with non-bound LDL), increased electrophoretic mobility (by 40-50%), increased hydrated density (difference in modae, 5.6-5.9 mg/mL), and smaller particle size (difference in modae, 3.8-4.9 nm). Bound LDL possessed the ability to induce a 2.1- to 2.7-fold increase in intracellular cholesterol content.

Conclusion: The results showed the presence of a dense, small, more electronegative, desialylated LDL subfraction in the blood of diabetic patients, which is in vivo modified atherogenic LDL.

Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles.

Cardiac muscle contraction is a strictly regulated process which conjugates a series of electrophysiological, biochemical and mechanic events, resulting in the pumping of blood to all bodily tissues. These phenomena require a very high energetic demand both for generating the necessary mechanical force, and for maintaining cellular homeostasis during the process. In the myocardium, fatty acids (FA) represent the main energy substrate, although other secondary substrates, such as glucose and ketone bodies, may also be used. Nevertheless, under certain conditions such as heart failure or myocardial ischemia, FA metabolism may become deleterious via mechanisms such as oxidative stress and arrhythmogenesis. In an ischemic milieu, various metabolic changes occur as a consequence of hypoxia, favoring cell necrosis, ventricular arrhythmias, and death. Major events in this context include an increase in extracellular K⁺, a decrease in pH, and accumulation of intracellular calcium. This review includes a detailed description of the molecular basis underlying myocardial contraction and energetic metabolism in cardiomyocytes, aiming to promote an integral understanding of the pathophysiology of heart ischemia. This in turn may aid in the development of future, more satisfactory alternative treatments in the management of acute coronary ischemia episodes.

Extracorporeal blood purification is becoming increasingly important in intensive therapy for multiple organ dysfunction syndrome (MODS) and sepsis, considering all of their pathophysiological aspects. The results of treatment, particularly in children, considering their anatomical and physiological features, are related to the severity and progression of organ failure, the indications that are found, the choice of method, and the timely initiation of blood purification. Multiple organ support therapy is the aim of introducing and applying blood purification today. Various extracorporeal blood purification techniques directly affect the molecular and electrolyte composition of blood and influence all structures of the human body, which can allow us to correct, recover, replace and maintain homeostasis in MODS. The potential of new extracorporeal molecular technologies allows their successful use in severe cardiac and respiratory failure, acute kidney injury and hepatic dysfunction and in complex therapy for severe infections and sepsis and extreme metabolic violations. Adult and pediatric patients after cardiac surgery with cardiopulmonary bypass form a special cohort that often requires the application of various intra- and extracorporeal techniques due to the development of MODS, infections and sepsis in the postoperative period.

Leriche’s syndrome is an aortic occlusive disease, which is due to obliteration of distal aorta above the site of bifurcation of common iliac arteries. The classic triad of symptoms include claudication, impotence, and absent or decreased femoral pulses. It may be acute or chronic in onset. Most of the cases are chronic in nature due to baseline pathophysiology involving atherosclerotic changes in the aorta. There are many causes of acute leriche’s syndrome like surgical manipulation, trauma, thromboembolic disease, hypercoagulability, atrial fibrillation, neoplasm, intraplaque hemorrhage in an aneurysm. Post-surgical Leriche’s syndrome is rare and needs a strong index of suspicion to diagnose. The authors highlight a case of Leriche’s syndrome, as a post-surgical complication and its clinical importance.

Aim: This paper aims to compare the mechanical performance of metallic (Xience) and bioresorbable polymeric (Elixir) stents during the process of crimping and deployment.

Methods: Finite element software ABAQUS was used to create the geometrical models and meshes for the balloon, stent and diseased artery. To simulate the crimping of stents, 12 rigid plates were generated around the stent and subjected to radially enforced displacement. The deployment of both stents was simulated by applying internal pressure to the balloon, where hard contacts were defined between balloon, stent and diseased artery.

Results: Elixir stent exhibited a lower expansion rate than Xience stent during deployment. The stent diameter achieved after balloon deflation was found smaller for Elixir stent due to higher recoiling. Lower level of stresses was found in the plaque and artery when expanded by Elixir stent. Reduced expansion, increased dogboning and decreased vessel stresses were obtained when considering the crimping-generated residual stresses in the simulations.

Conclusion: There is a challenge for polymeric stents to match the mechanical performance of metallic stents. However, polymeric stents impose lower stresses to the artery system due to less property mismatch between polymers and arterial tissues, which could be clinically beneficial.

Cerebral cavernous malformations (CCM) are manifested by microvascular lesions characterized by leaky endothelial cells with minimal intervening parenchyma predominantly in the central nervous system predisposed to hemorrhagic stroke, resulting in focal neurological defects. Till date, three proteins are implicated in this condition: CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10). These multi-domain proteins form a protein complex via CCM2 that function as a docking site for the CCM signaling complex, which modulates many signaling pathways. Defects in the formation of this signaling complex have been shown to affect a wide range of cellular processes including cell-cell contact stability, vascular angiogenesis, oxidative damage protection and multiple biogenic events. In this review we provide an update on recent advances in structure and function of these CCM proteins, especially focusing on the signaling cascades involved in CCM pathogenesis and the resultant CCM cellular phenotypes in the past decade.

Depression is one of the most common psychiatric disorders, and has become an epidemic in modern medical practice; notorious for frequently co-occurring with multiple comorbidities, especially cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and its various risk factors comprised in the metabolic syndrome (MS). Selective serotonin reuptake inhibitors (SSRIs) are the most widely used class of psychotropic drugs in this and many other clinical scenarios; yet their impact on cardiometabolic health has not been elucidated. The objective of this review was to summarize current views on the pharmacology of SSRIs and cardiometabolic risk, as well as available epidemiological evidence regarding its clinical significance. SSRIs appear to intervene in cardiometabolic physiology fundamentally by modulating chronic inflammation, a key pathophysiologic phenomenon in MS, DM2 and CVD. However, the dosing necessary to achieve a beneficial impact in this regard, as well as their clinical correlations, remain controversial. Each SSRI displays a particular profile regarding each of the components of the MS: weight gain seems to be the most common effect of SSRIs, more frequent with paroxetine, followed by citalopram and escitalopram. As a drug class, SSRIs also appear to promote hypercholesterolemia rather uniformly, while fluoxetine and citalopram appear to particularly increase triacylglyceride levels. In contrast, fluvoxamine and paroxetine seem to have the greatest impact on dysglycemia. Lastly, most SSRIs appear to be innocuous or even beneficial regarding blood pressure and high-density lipoprotein cholesterol. Nevertheless, many of these effects may vary significantly upon specific clinical circumstances, especially timing. This topic remains rather unexplored in clinical psychopharmacology, and further, larger-scale epidemiological studies are needed in order to offer improved care in this field.

Pathological vascular remodeling is observed in various cardiovascular diseases including pulmonary hypertension (PH), a disease of unknown etiology that has been characterized by pulmonary artery vasoconstriction, right ventricular hypertrophy, vascular inflammation, and abnormal angiogenesis in pulmonary circulation. G protein-coupled receptors (GPCRs) are the largest family in the genome and widely expressed in cardiovascular system. They regulate all aspects of PH pathophysiology and represent therapeutic targets. We overview GPCRs function in vasoconstriction, vasodilation, vascular inflammation-driven remodeling and describe signaling cross talk between GPCR, inflammatory cytokines, and growth factors. Overall, the goal of this review is to emphasize the importance of GPCRs as critical signal transducers and targets for drug development in PH.

Aim: The circadian clock is a molecular network that controls the body physiological rhythms. In blood vessels, the circadian clock components modulate vascular remodeling, blood pressure, and signaling. The goal in this study was to determine the pattern of expression of circadian clock proteins in the endothelium, smooth muscle, and adventitia of the vasculature of human and mouse tissues.

Methods: Immunohistochemistry was performed in frozen sections of mouse aorta, common carotid artery, femoral artery, lung, and heart at 12 AM and 12 PM for Bmal1, Clock, Npas2, Per and other clock components. Studies of expression were also assessed in human saphenous vein both by immunoblotting and immunohistochemistry.

Results: In this study, we identified the expression of Bmal1, Clock, Npas, Per1, Cry1, and accessory clock components by immunohistochemical staining in the endothelium, smooth muscle and adventitia of the mouse vasculature with differing temporal and cellular profiles depending on vasculature and tissue analyzed. The human saphenous vein also exhibited expression of clock genes that exhibited an oscillatory pattern in Bmal1 and Cry by immunoblotting.

Conclusion: These studies show that circadian clock components display differences in expression and localization throughout the cardiovascular system, which may confer nuances of circadian clock signaling in a cell-specific manner.

Bioresorbable stents (BRSs) are regarded as the next-generation medical devices to treat blocked or diseased arteries. The use of BRSs aims to reduce the risk of late stent thrombosis and long-term tissue inflammation associated with permanent metallic stents. BRSs are designed to relieve symptoms immediately and also provide mechanical support for an appropriate time period before they are fully absorbed by human body. To promote clinical adoption of BRSs or even to substitute metallic stents, the mechanical performance of BRSs needs to be thoroughly investigated and quantitatively characterised, especially over the full period of degradation. This paper offers a review of current research status of polymeric BRSs, covering both experimental and modelling work. Review of experimental studies highlighted the effects of stent designs and materials on the behaviour of polymeric BRSs. Computational work was able to simulate crimping, expansion and degradation of polymeric BRSs and the results were useful for performance assessment. In summary, the development of polymeric BRSs is still at an early stage, and further research is urgently required for a better understanding and control of their mechanical performance.

Aim: This study was designed to evaluate the effects of dietary and lifestyle habits on several blood lipid parameters in the Lebanese population.

Methods: This was a cross-sectional study for 2,000 individuals, of whom 1,003 completed the survey about their dietary and lifestyle habits. Anthropometric measurements and blood tests were performed and recorded.

Results: Up to 53.2% of the population was hypercholesterolemic. Gender and age contributed to the prevalence of high levels of low density lipoprotein cholesterol (LDL-C) or triglycerides. Prevalence of hypercholesterolemia, hypertriglyceridemia and high LDL-C levels was higher in smokers, physically inactive or those who consume fatty meat or eggs. Prevalence of hypercholesterolemia was not affected by consumption of whole milk, skimmed milk or fruits and vegetables. However, the prevalence of hypertriglyceridemia and high LDL-levels was higher in individuals who consumed whole milk, and lower in those who consumed skimmed or fruits and vegetables.

Conclusion: Hyperlipidemia affects more than half of the Lebanese population. The finding that the majority of the individuals were unaware of their lipid profile mandates warrant efforts for both patient and public education.

Atherosclerosis and related cardiovascular disorders remain the leading global cause of morbidity and mortality. Modified low density lipoprotein (LDL) is considered to play a crucial role in atherosclerosis development. During the past decades, several types of atherogenic LDL modification have been discovered. Desialylation was one of the atherogenic modifications observed in circulating atherogenic LDL in vivo. Sialic acid level negatively correlates with triglyceride and cholesterol contents. Desialylated LDL is small, dense and highly susceptible to oxidation, as reported for hyperlipidemic conditions. This atherogenic modification leads to increased cholesterol intake by macrophages and smooth-muscle cells, and is also associated with other pathologies, such as diabetes mellitus. Moreover, these conditions provoke damage and desialylated LDL particles may trigger autoimmune reactions in macrophages and B-cells.

Aim: This study was undertaken to test the hypothesis that insulin treatment has unexpected pro-atherogenic effects at the cellular level, namely, proliferative activity and intracellular cholesterol content.

Methods: Primary cultures of subendothelial cells derived from non-atherosclerotic human aorta and mouse peritoneal macrophages were used to investigate the in vitro effect of insulin on atherosclerosis-related parameters, such as cellular cholesterol content and proliferation rate. Additionally, the effect of insulin treatment in 33 type 1 diabetic patients on serum atherogenicity (i.e. its ability to induce cholesterol accumulation in cultured cells) was investigated.

Results: Insulin (1-1,000 µU/mL) did not affect [³H]-thymidine incorporation or cholesterol content in either type of cultured cell. Most blood sera obtained from type 1 diabetic patients induced a 1.5- to 1.7-fold increase in cholesterol content of cultured cells, but this effect did not correlate with serum insulin levels. Exogenous insulin added to cultured cells did not modify the effect of patient's sera on cholesterol level and proliferation of cultured cells.

Conclusion: The results suggest that insulin does not exert direct atherogenic actions at the level of arterial cells, with the respect to proliferative activity and cholesterol content.

Aim: The aim of the present article was the detection of threshold heteroplasmy level of mitochondrial DNA mutations, above which a patient is at increased risk of atherosclerotic lesions. Besides, this parameter was detected for mutations, in which after reaching threshold heteroplasmy level, a protective antiatherogenic effect started to appear.

Methods: The participants of the study were 700 women and men from the Moscow region. Fragments of DNA, amplified by polymerase chain reaction, were analyzed with pyrosequencing technology. Then on the basis of pyrograms’ peaks in the samples, the heteroplasmy level of the investigated mitochondrial genome mutations was detected.

Results: The threshold heteroplasmy level of 11 investigated mutations (m.5178C>A, m.15059G>A, m.652delG, m.13513G>A, m.14846G>A, m.652insG, m.12315G>A, m.3336T>C, m.1555A>G, m.14459G>A, m.3256C>T) in individuals with atherosclerotic plaques or thickening of the intima-medial layer of carotid arteries was detected.

Conclusion: Using the method developed in our laboratory, the authors managed to determine threshold heteroplasmy levels of 11 mitochondrial genome mutations associated with atherosclerosis. The authors suggest that threshold heteroplasmy levels of these mutations is a new criterion for evaluation of predisposition to the occurrence and development of atherosclerotic lesions in human arteries.

Aim: To assess the value of body mass index (BMI) and adipokine levels in predicting development of atrial fibrillation (AF) in the general population.

Methods: Three hundred and ninety eight patients were examined for the presence of phenotype metabolically healthy obesity (MHO), according to the Wildman criteria; adipokine levels were assessed by enzyme immunoassay method; AF was assessed by electrocardiography (ECG) and/or by ECG diurnal monitoring.

Results: Obesity (group 1) and overweight (group 2) was present in 23.7% and 42.0% of participants; while 21.1% were normal body weight (group 3) and 13.1% had a BMI < 19.9 kg/m² (group 4). Phenotype MHO was detected in 19.6% patients. At follow-up, 32.4% of participants developed AF. Adiponectin levels were significantly higher in MHO patients as compared to metabolically unhealthy patients with abdominal obesity (AO). High molecular weight adiponectin (HMVAN) levels were significantly decreased in patients of groups 1 and 4, as compared to groups 2 and 3. Correlation between AF and HMWAN was determined by regressive analysis in patients of 1st and 4th groups (β = -0.24, P = 0.003 and β = -0.26, P = 0.002, respectively).

Conclusion: The probability of developing AF increases with AO and decreased BMI, which is accompanied by a change in HMVAN levels. In MHO patients, the probability of AF developing is identical with persons having normal BMI.