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: 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: To determine whether plasmatic biomarkers correlate with ¹⁸fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET-CT) and presence of microembolic signals (MES) detected by transcranial Doppler in patients with carotid stenosis.

Methods: ¹⁸FDG-PET-CT and MES detection was performed in consecutive patients with 50% to 99% symptomatic or asymptomatic carotid stenosis. Uptake index was defined by a target to background ratio (TBR) between maximum standardized uptake value of the carotid plaque and the average uptake of the jugular veins. The analysis of biomarkers included adhesion molecules [intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule 1, P-selectin and E-selectin], interleukins (IL-1, IL-6), chemokines (RANTES, monocyte chemoattractant protein 1), cytokines (tumor necrosis factor α), matrix-metalloproteases (MMP), myeloperoxidase, and lipoprotein-associated phospholipase A2.

Results: There were 54 symptomatic and 57 asymptomatic patients. TBR values were significantly higher in the symptomatic compared to the asymptomatic (median 2.1 vs. 1.8, P = 0.002) and in the MES positive (MES+) compared to the MES negative (MES-) group (MES+, n = 19, median 2.3 and MES-, n = 88, median 1.8, P = 0.01). The best threshold for TBR values was of 1.9. We found a significant correlation between higher ¹⁸FDG uptake (TBR ≥ 1.9) and the plasmatic levels of chemokine RANTES (P = 0.03) and higher levels of ICAM-1 in MES+ patients (P = 0.03). Interestingly MMP-2 levels were more important in patients with lower TBR values (P = 0.02) and MMP-3 and P-selectin in those who were MES- (respectively P = 0.001 and P = 0.009).

Conclusion: In the present study, ICAM-1 was associated with the presence of thrombotically active atherosclerotic plaques, while RANTES mainly correlated with the inflammatory process. MMP-2, MMP-3 and P-selectin levels were more important in patients with stable plaques.

Aim: This paper aims to evaluate the effectiveness of MitraClip implantation as a solution to severe mitral regurgitation (MR) in the case of posterior leaflet prolapse due to hypertrophic obstructive cardiomyopathy and chordae rupture.

Methods: NX CAD software was used to create a surface geometric model for the mitral valve (MV). A hyperelastic material model, calibrated against experimental results, was used to describe stress-strain responses of the MV leaflets, and a spring element approach was used to describe chordae response. Abaqus CAE was employed to create a finite element model for diseased MV suffering from MR. The effectiveness of MitraClip implantation on valve function was investigated by simulating the deformation of diseased valve, with and without MitraClip repair, during peak systole and diastole. Leaflet deformation and stress distributions were used to assess the effectiveness of the procedure.

Results: Overall, significant improvement was achieved for the diseased valve after MitraClip implantation. Prior to the introduction of the clip, the diseased valve was subjected to posterior leaflet prolapse which would induce a jet of MR. Once the MitraClip was included in the simulation, the valve leaflets were able to close and seal off, almost entirely at peak systolic condition without a significant impact on the stress distribution of the valve leaflets.

Conclusion: The results in this study provide further evidence to support MitraClip repair as a viable treatment for high-risk patients suffering from severe MR, and also highlight the need for further research into such an advanced, minimally invasive surgery technique.

Descending thoracic aortic aneurysm management has gained momentum and became a topic of many debates at international levels since the evolution of endovascular repair. Ruptured descending thoracic aortic aneurysm is a clinical emergency which is associated with high mortality and morbidity rates if not managed properly. Prior to thoracic endovascular aortic repair (TEVAR), open repair (OR) was the gold standard management, however since the evolution of TEVAR, this has changed. Several centers have reported many of their experiences and published that TEVAR can provide equal or even better perioperative outcomes when compared to OR, although the evidences can be of only short term and could be biased at different levels at the time of publication. This review article is aimed to examine current literature evidences behind the use of TEVAR vs. OR and the reported comparative clinical outcomes.

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.

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.

Descending thoracic aortic aneurysm management has gained momentum and became a topic of many debates at international levels since the evolution of endovascular repair. Ruptured descending thoracic aortic aneurysm is a clinical emergency which is associated with high mortality and morbidity rates if not managed properly. Prior to thoracic endovascular aortic repair (TEVAR), open repair (OR) was the gold standard management, however since the evolution of TEVAR, this has changed. Several centers have reported many of their experiences and published that TEVAR can provide equal or even better perioperative outcomes when compared to OR, although the evidences can be of only short term and could be biased at different levels at the time of publication. This review article is aimed to examine current literature evidences behind the use of TEVAR vs. OR and the reported comparative clinical outcomes.

Aim: To determine whether plasmatic biomarkers correlate with ¹⁸fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET-CT) and presence of microembolic signals (MES) detected by transcranial Doppler in patients with carotid stenosis.

Methods: ¹⁸FDG-PET-CT and MES detection was performed in consecutive patients with 50% to 99% symptomatic or asymptomatic carotid stenosis. Uptake index was defined by a target to background ratio (TBR) between maximum standardized uptake value of the carotid plaque and the average uptake of the jugular veins. The analysis of biomarkers included adhesion molecules [intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule 1, P-selectin and E-selectin], interleukins (IL-1, IL-6), chemokines (RANTES, monocyte chemoattractant protein 1), cytokines (tumor necrosis factor α), matrix-metalloproteases (MMP), myeloperoxidase, and lipoprotein-associated phospholipase A2.

Results: There were 54 symptomatic and 57 asymptomatic patients. TBR values were significantly higher in the symptomatic compared to the asymptomatic (median 2.1 vs. 1.8, P = 0.002) and in the MES positive (MES+) compared to the MES negative (MES-) group (MES+, n = 19, median 2.3 and MES-, n = 88, median 1.8, P = 0.01). The best threshold for TBR values was of 1.9. We found a significant correlation between higher ¹⁸FDG uptake (TBR ≥ 1.9) and the plasmatic levels of chemokine RANTES (P = 0.03) and higher levels of ICAM-1 in MES+ patients (P = 0.03). Interestingly MMP-2 levels were more important in patients with lower TBR values (P = 0.02) and MMP-3 and P-selectin in those who were MES- (respectively P = 0.001 and P = 0.009).

Conclusion: In the present study, ICAM-1 was associated with the presence of thrombotically active atherosclerotic plaques, while RANTES mainly correlated with the inflammatory process. MMP-2, MMP-3 and P-selectin levels were more important in patients with stable plaques.

Aim: This paper aims to evaluate the effectiveness of MitraClip implantation as a solution to severe mitral regurgitation (MR) in the case of posterior leaflet prolapse due to hypertrophic obstructive cardiomyopathy and chordae rupture.

Methods: NX CAD software was used to create a surface geometric model for the mitral valve (MV). A hyperelastic material model, calibrated against experimental results, was used to describe stress-strain responses of the MV leaflets, and a spring element approach was used to describe chordae response. Abaqus CAE was employed to create a finite element model for diseased MV suffering from MR. The effectiveness of MitraClip implantation on valve function was investigated by simulating the deformation of diseased valve, with and without MitraClip repair, during peak systole and diastole. Leaflet deformation and stress distributions were used to assess the effectiveness of the procedure.

Results: Overall, significant improvement was achieved for the diseased valve after MitraClip implantation. Prior to the introduction of the clip, the diseased valve was subjected to posterior leaflet prolapse which would induce a jet of MR. Once the MitraClip was included in the simulation, the valve leaflets were able to close and seal off, almost entirely at peak systolic condition without a significant impact on the stress distribution of the valve leaflets.

Conclusion: The results in this study provide further evidence to support MitraClip repair as a viable treatment for high-risk patients suffering from severe MR, and also highlight the need for further research into such an advanced, minimally invasive surgery technique.

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.

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.

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 aim of this pilot study was to compare the heteroplasmy levels of specific mitochondrial (mt)DNA mutations in human buccal epithelial and whole blood cells in participants with different degrees of predisposition to atherosclerosis. The potential for buccal epithelium to be used for the genetic diagnosis of atherosclerosis using mtDNA mutations was assessed.

Methods: Samples of buccal epithelial and whole blood cells were obtained from 134 donors. DNA was extracted from the samples and subjected to polymerase chain reaction and pyrosequencing. The threshold heteroplasmy levels of the mutations m.12315G>A, m.3336T>C, m.1555А>G, m.13513G>A, and m.3256C>T were analyzed in order to assess the potential for using buccal epithelium and whole blood for the genetic diagnosis of atherosclerosis.

Results: The threshold heteroplasmy levels of the assessed mitochondrial mutations did not significantly differ between buccal epithelial and whole blood cells.

Conclusion: Buccal epithelial cells may be preferable to whole blood cells for analyzing the association of mitochondrial genome mutations with atherosclerosis.

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 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.