Is There a Need for Sex-Tailored Lipoprotein(a) Cut-Off Values for Coronary Artery Disease Risk Stratification?

BACKGROUND: Lipoprotein(a) [Lp(a)] plasma level is a well-known risk factor for coronary artery disease (CAD). Existing data regarding the influence of sex on the Lp(a)-CAD relationship are inconsistent. OBJECTIVE: To investigate the relationship between Lp(a) and CAD in men and women and to elucidate any sex-specific differences that may exist. METHODS: Data of patients with Lp(a) measurements who were admitted to a tertiary university hospital, Koc University Hospital, were analyzed. The relationship between Lp(a) levels and CAD was explored in all patients and in subgroups created by sex. Two commonly accepted Lp(a) thresholds ≥ 30 and ≥ 50 mg/dL were analyzed. RESULTS: A total of 1858 patients (mean age 54 ± 17 years; 53.33% females) were included in the analysis. Lp(a) was an independent predictor of CAD according to the multivariate regression model for the entire cohort. In all cohort, both cut-off values (≥ 30 and ≥ 50 mg/dL) were detected as independent predictors of CAD (p < 0.001). In sex-specific analysis, an Lp(a) ≥ 30 mg/dL was an independent predictor of CAD only in women (p < 0.001), but Lp(a) ≥ 50 mg/dL was a CAD predictor both in men and women (men, p = 0.004; women, p = 0.047). CONCLUSION: The findings of this study may suggest that different thresholds of Lp(a) level can be employed for risk stratification in women compared to men.

Exosomes encapsulated in hydrogels for effective central nervous system drug delivery.

The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions. The therapeutic effect of active biomolecules is significantly impaired after systemic administration in the central nervous system (CNS) because of the blood-brain barrier (BBB). Therefore, the development of novel therapeutic approaches capable of overcoming these limitations is under discussion. Exosomes (Exo) are nano-sized vesicles of endosomal origin that have a high distribution rate in biofluids. Recent advances have introduced Exo as naturally suitable bio-shuttles for the delivery of neurotrophic factors to the brain parenchyma. In recent years, many researchers have attempted to regulate the delivery of Exo to target sites while reducing their removal from circulation. The encapsulation of Exo in natural and synthetic hydrogels offers a valuable strategy to address the limitations of Exo, maintaining their integrity and controlling their release at a desired site. Herein, we highlight the current and novel approaches related to the application of hydrogels for the encapsulation of Exo in the field of CNS tissue engineering.

MRI diagnosed cardiac lipoma in tuberous sclerosis: a case report with a very rare association.

Tuberous sclerosis is a genetic multisystem disorder characterised by hamartomas in several organs. Cardiac rhabdomyomas are the main features of the disease but lipomas can very rarely be associated. Herein, we present a very rare association of tuberous sclerosis and cardiac lipoma detected by echocardiography and diagnosed as a lipoma via MRI and fat suppression technic, aim to report this very rare association, and emphasise usefulness of MRI in cardiac mass lesions.

An Easy-to-Fabricate Microfluidic Shallow Trench Induced Three-Dimensional Cell Culturing and Imaging (STICI3D) Platform.

Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable nature of the STICI3D platform makes it suitable for researchers interested in fabricating custom polydimethylsiloxane devices as well as those who are in need of ready-to-use plastic platforms. As such, STICI3Ds can be used in imaging cell-cell interactions, angiogenesis, semiquantitative analysis of drug response in cells, and measurement of transport through cell sheet barriers.

A new association of Oculoauriculovertebral spectrum and persistent fifth aortic arch -double lumen aorta: a case report.

BACKGROUND: Oculo-auriculo-vertebral spectrum is a heterogeneous group of genetic disorder, also known as Goldenhar Syndrome, which has several phenotypic features including craniofacial anomalies, cardiac, vertebral and central nervous system defects. Cardiovascular anomalies include ventricular septal defects, atrial septal defects, patent ductus arteriosus, Tetralogy of Fallot, double outlet right ventricle, aberrant right subclavian artery, coarctation of aorta, transposition of the great arteries, double inlet left ventricle, cor triatriatum, pulmonary artery stenosis, aortic stenosis, persistent left superior vena cava, partially or totally abnormal pulmonary venous return and bicuspid aortic valve. Persistent fifth aortic arch, also named as double lumen aortic arch, is a very rare cardivascular anomaly and usually associate other cardiac defects. CASE PRESENTATION: We present a 7 month old patient with oculo-auriculo-vertebral spectrum signs as facial asymmetry, short neck, choanal atresia, cleft palate, bilateral preauricular skin tags, bilateral hypoplastic ear lobes, epibulbar dermoid cyst, rib, vertebrae and cardiovascular anomalies. Cardiovascular anomalies detected with echocardiography and computed tomography were malalignment ventricular septal defect and double lumen aorta, known as persistent fifth aortic arch. CONCLUSION: Various cardiovascular anomalies may accompany Goldenhar Syndrome. We present a case with persistent fifth aortic arch and Oculo-auriculo-vertebral spectrum and this is a new association that was not reported before in the literature.

The effects of pre-pregnancy obesity and gestational weight gain on maternal lipid profiles, fatty acids and insulin resistance.

OBJECTIVES: Pregnancy is associated with physiological alterations in insulin sensitivity and lipid metabolism. This study investigates the associations between pregestational body mass index (pBMI) and the rate of gestational weight gain (rGWG) in the second trimester with the biomarkers of lipid, fatty acids metabolism and insulin resistance. METHODS: Sixty nine pregnant women followed. The body weights of the pregnant women were measured and blood samples were obtained at 11-14th and 24-28th weeks of pregnancy. Glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, insulin levels and fatty acids were measured. Rate of GWG (kg/week) and The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were calculated. The pregnant women were stratified according to their pBMI and the 2nd trimester rGWG. RESULTS: The rate of GWG was significantly higher for the group with pBMI<25, compared to the group with pBMI≥25 (p=0.024). Triglyceride, total cholesterol, LDL and HDL cholesterol were significantly increased in the second trimester compared with the first trimester. Palmitic acid, oleic acid, linoleic acid, myristic acid, docosahexaenoic acid (DHA), arachidonic acid (AA), total omega-6 (n - 6) and omega-3 (n - 3) fatty acid levels and n - 6/n - 3 ratio were significantly higher in the second trimester. Glucose was significantly decreased and insulin was increased in the second trimester. In the overweight/obese group; HOMA-IR, insulin, AA, palmitoleic acid and stearic acid were found to be high in comparison to the group with low/normal pBMI. No parameters were associated with rGWG. CONCLUSIONS: The changes in lipid parameters, free fatty acids, insulin and HOMA-IR in the second trimester were compatible with the changes in lipid metabolism and the development of insulin resistance. Pregestational BMI was shown to have a stronger influence on lipid profile, insulin resistance, and fatty acids than rGWG.

An Update on the Role of PCSK9 in Atherosclerosis.

Atherosclerosis is initiated by functional changes in the endothelium accompanied by accumulation, oxidation, and glycation of LDL-cholesterol in the inner layer of the arterial wall and continues with the expression of adhesion molecules and release of chemoattractants. PCSK9 is a proprotein convertase that increases circulating LDL levels by directing hepatic LDL receptors into lysosomes for degradation. The effects of PCSK9 on hepatic LDL receptors and contribution to atherosclerosis via the induction of hyperlipidemia are well defined. Monoclonal PCSK9 antibodies that block the effects of PCSK9 on LDL receptors demonstrated beneficial results in cardiovascular outcome trials. In recent years, extrahepatic functions of PCSK9, particularly its direct effects on atherosclerotic plaques have received increasing attention. Experimental trials have revealed that PCSK9 plays a significant role in every step of atherosclerotic plaque formation. It contributes to foam cell formation by increasing the uptake of LDL by macrophages via scavenger receptors and inhibiting cholesterol efflux from macrophages. It induces the expression of inflammatory cytokines, adhesion molecules, and chemoattractants, thereby increasing monocyte recruitment, inflammatory cell adhesion, and inflammation at the atherosclerotic vascular wall. Moreover, low shear stress is associated with increased PCSK9 expression. PCSK9 may induce endothelial cell apoptosis and autophagy and stimulate the differentiation of smooth muscle cells from the contractile phenotype to synthetic phenotype. Increasing evidence indicates that PCSK9 is a molecular target in the development of novel approaches toward the prevention and treatment of atherosclerosis. This review focuses on the molecular roles of PCSK9 in atherosclerotic plaque formation.

Is N-terminal pro-brain natriuretic peptide a reliable marker for body fluid status in children with chronic kidney disease?

INTRODUCTION: Brain natriuretic peptides, released in response to left ventricular stress, have a strong prognostic value in dialysis patients. However, their role in detecting abnormalities of fluid status is under debate; the relationship between volume status and brain natriuretic peptides (BNPs) differs among various studies. The aim of our study was to evaluate the clinical utility of N-terminal proBNP in the assessment of fluid status and cardiovascular risk in this setting. MATERIAL AND METHODS: The study included 65 children: 10 pre-dialysis, 13 hemodialysis, 12 peritoneal dialysis patients and 30 healthy controls. Volume status was determined by multifrequency bioimpedance and NT-pro-BNP, as well as echocardiography to estimate the left ventricle structure and function. RESULTS: The median log NT-proBNP values of hemodialysis and peritoneal dialysis patients were 3.66 (2.05-4.90) and 3.57 (2.51-4.13) pg/ml, respectively, and significantly higher compared with the control group (p < 0.001, p < 0.001). On simple correlation, NT-proBNP was correlated with markers of volume overload and cardiac dysfunction. On multivariate regression analysis, only left ventricle mass index (ß = 0.402, p = 0.003) and left atrium diameter (ß = 0.263, p = 0.018) were independently associated with NT-proBNP (adjusted R 2 of the model: 0.707, p < 0.001). CONCLUSIONS: Our research suggested that NT-proBNP, which was correlated with LV systolic and diastolic dysfunction and fluid overload as assessed by bioimpedance, can be used to evaluate cardiovascular states in a chronic kidney disease (CKD) population. From the early stages of CKD, periodic monitoring of NT-proBNP levels may be essential for early detection of patients with high risk of cardiovascular events, and for taking preventive intervention as soon as possible.

Cardiac functions in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: The aim of the present study was to evaluate the presence of cardiac systolic and diastolic dysfunction in pediatric patients with steroid-sensitive nephrotic syndrome (NS). METHODS: The study population consisted of 19 patients with debut-relapse of NS aged 1-18 years and 30 sex and age-matched healthy controls. Blood and urine samples, two M-mode conventional echocardiograms and tissue Doppler velocity imaging were evaluated in both attack and remission periods. RESULTS: With regard to conventional pulse wave Doppler (cPWD), steroid-sensitive NS patients (both in debut / relapse and in remission periods) had a higher peak of late diastolic flow velocities (A peak), and patients in debut / relapse had a lower E/A ratio than the control group, indicating diastolic dysfunction (overall P = 0.003 and P = 0.006, respectively). Based on tissue Doppler velocity imaging echocardiography results, patients in debut/relapse had a higher A' and a lower E'/A' ratio (overall P < 0.001 and P = 0.001, respectively). There was also a significant difference in the cPWD E/TDI E' ratio between the patients showing an increased cPWD E/TDI E' ratio in remission periods compared to in debut/relapse periods (P = 0.09). The albumin levels were positively correlated with E'/A' and E/ E' ratio (r = 0.609; P = 0.007, r = 0.472; P = 0.041 respectively). CONCLUSIONS: Systolic cardiac functions are preserved but diastolic functions are affected in steroid-sensitive NS patients both in debut/relapse and in remission periods in a relatively short time. The persistence of left ventricular (LV) dysfunction during the remission period requires special attention during the follow up for early detection of cardiac abnormalities.

The anti-angiogenic potential of (±) gossypol in comparison to suramin.

Cotton, a staple fiber that grows around the seeds of the cotton plants (Gossypium), is produced throughout the world, and its by products, such as cotton fibers, cotton-seed oil, and cottonseed proteins, have a variety of applications. Cotton-seed contains gossypol, a natural phenol compound. (±)-Gossypol is a yellowish polyphenol that is derived from different parts of the cotton plant and contains potent anticancer properties. Tumor growth and metastasis are mainly related to angiogenesis; therefore, anti-angiogenic therapy targets the new blood vessels that provide oxygen and nutrients to actively proliferating tumor cells. The aim of the present study was to evaluate the anti-angiogenic potential of (±)-gossypol in vitro. (±)-Gossypol has anti-proliferative effects on cancer cell lines; however, its anti-angiogenic effects on normal cells have not been studied. Anti-proliferative activities of gossypol assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, anti-angiogenic activities using tube formation assay, and cell migration inhibition capability using a wound-healing assay on human umbilical vein endothelial cells (HUVECs) were revealed. (±)-Gossypol displayed the following potent anti-angiogenic activities in vitro: it inhibited the cell viability of HUVECs, it inhibited the migration of HUVECs, and disrupted endothelial tube formation in a dose-dependent manner. In addition, the anti-angiogenic effects of (±)-gossypol were investigated in ovo in a model using a chick chorioallantoic membrane (CAM). Decreases in capillary density were assessed and scored. (±)-Gossypol showed dose-dependent anti-angiogenic effects on CAM. These findings suggest that (±)-gossypol can be used as a new anti-angiogenic agent.