Hemocompatibility Evaluation of Thai Bombyx mori Silk Fibroin and Its Improvement with Low Molecular Weight Heparin Immobilization.

Bombyx mori silk fibroin (SF), from Nangnoi Srisaket 1 Thai strain, has shown potential for various biomedical applications such as wound dressing, a vascular patch, bone substitutes, and controlled release systems. The hemocompatibility of this SF is one of the important characteristics that have impacts on such applications. In this study, the hemocompatibility of Thai SF was investigated and its improvement by low molecular weight heparin (LMWH) immobilization was demonstrated. Endothelial cell proliferation on the SF and LMWH immobilized SF (Hep/SF) samples with or without fibroblast growth factor-2 (FGF-2) was also evaluated. According to hemocompatibility evaluation, Thai SF did not accelerate clotting time, excess stimulate complement and leukocyte activation, and was considered a non-hemolysis material compared to the negative control PTFE sheet. Platelet adhesion of SF film was comparable to that of the PTFE sheet. For hemocompatibility enhancement, LMWH was immobilized successfully and could improve the surface hydrophilicity of SF films. The Hep/SF films demonstrated prolonged clotting time and slightly lower complement and leukocyte activation. However, the Hep/SF films could not suppress platelet adhesion. The Hep/SF films demonstrated endothelial cell proliferation enhancement, particularly with FGF-2 addition. This study provides fundamental information for the further development of Thai SF as a hemocompatible biomaterial.

The protective effects of reparixin against endothelial ischemia-reperfusion injury.

Objectives: Myocardial ischemia is a lack of blood supply to myocardial tissue. Rapid reperfusion therapy is required to prevent myocardial infarction. However, ischemia and reperfusion contribute to myocardial and endothelial injury or ischemia-reperfusion injury (IRI). A pro-inflammatory cytokine interleukin-8 (IL-8/CXCL8) plays an important role in the activation of neutrophil accumulation and promotes endothelial dysfunction. Therefore, inhibition of IRI through the regulation of inflammation using a CXCL8 receptor inhibitor reparixin is an attractive target. The aim of this study is to evaluate the effect of reparixin on endothelial cell viability after IRI. Methods: Human vascular endothelial cells (EA.hy926) were cultured and pretreated with reparixin at concentrations of 0-1 mg/ml. To simulate ischemia, the cells were exposed to simulated ischemia solution for 60 min. Then, the cells were given complete medium as reperfusion followed by treatment with reparixin and incubated for 24 h. Cell viability was tested using MTT assay. Results: Percentages of cell viability of reparixin-treated groups of 0.0625 mg/mL (67.88 ± 7.82% control) and 0.125 mg/mL (84.28 ± 4.68% control) were significantly higher than that of the IR group (44.31 ± 4.64% control) at P < 0.05. The percentage of cell viability in the 0.125 mg/mL reparixin-treated group was not significantly different compared to the control. Conclusion: Pretreatment and treatment of endothelial cells with reparixin, which is a CXCL-8 receptor inhibitor, demonstrated a protective effect on cell viability after simulated ischemia-reperfusion. However, further studies to investigate the underlying mechanisms are needed.

The Relationship Between Glycemic Control and Concomitant Hypertension on Arterial Stiffness in Type II Diabetes.

PURPOSE: The impact of glycemic control on macrovascular complications and arterial stiffness in type II diabetes (T2D), as well as the extent of additive effect of hypertension, is unclear. The aims of this study were to investigate the impact of glycemic control on the cardio-ankle vascular index (CAVI), an indicator of arterial stiffness, and to determine the relative risk of concomitant diabetes and hypertension with arterial stiffness. METHODS: One hundred and nine participants were enrolled and classified as non-diabetes (n= 37) and diabetes (n=72); the diabetic group was further identified as controllable and uncontrollable T2D depending on their hemoglobin A1c (HbA1c) levels. Univariate and multiple regression analyses were used to assess the association between CAVI and glycemic control status and hypertension. Relative risk analysis for abnormal CAVI with exposure to diabetes and hypertension was investigated. RESULTS: In all participants, age, systolic blood pressure, body mass index, and fasting blood sugar were independent predictors of CAVI. In diabetic participants, glycemic control status or HbA1c levels did not significantly correlate with CAVI. Systolic blood pressure was an independent predictor for CAVI with ß = 0.26. In addition, the coexistence of diabetes together with hypertension was significantly associated with a 2.4-fold increase in the risk of abnormal CAVI (95% CI, 1.410-4.184; p <0.001). CONCLUSION: This study demonstrates that HbA1c as well as fasting blood sugar levels in diabetic participants do not correlate with arterial stiffness. Concomitant diabetes and hypertension significantly increase the risk of arterial stiffness.

Leptin Levels are Associated with Subclinical Cardiac Dysfunction in Obese Adolescents.

PURPOSE: The purposes of this study were to use speckle tracking echocardiography to confirm the influence of obesity on cardiac functions and to assess their relationships with leptin and uric acid levels in obese adolescents. METHODS: Eighty-one participants aged 16-19 years were recruited and classified as either non-obese (n = 30) or obese (n = 51). Global longitudinal strain (GLS), leptin and uric acid levels for each group were assessed and compared. The data from obese participants were then compared based on their leptin levels and analyzed for correlation using regression analysis. RESULTS: The obese group had significantly lower absolute GLS compared to the non-obese group (19.10 ± 0.30 versus 21.10 ± 0.30%, p < 0.001). In obese group, subclinical cardiac dysfunction was worse in the hyperleptinemic group than that of the normoleptinemic group (p = 0.03). Multivariate regression analysis showed that leptin and triglyceride levels were negatively associated with absolute GLS. Leptin could predict the absolute GLS with ß = -0.35 (p = 0.02). CONCLUSION: Subclinical left ventricular systolic dysfunction was found in obese adolescents, while GLS was worse in the hyperleptinemic subjects. Leptin, but not uric acid, levels were associated with a worsening of GLS.

Effects of high-intensity interval training on vascular function and maximum oxygen uptake in young sedentary females.

OBJECTIVE: Sedentary behavior is one of the risk factors for cardiometabolic diseases, including cardiovascular diseases, diabetes mellitus, and metabolic syndrome. High-intensity interval training (HIIT) is one effective way to reduce the risk of cardiometabolic diseases. This research studies the effects of cycling-based HIIT on vascular function and cardiorespiratory fitness in sedentary people. METHODS: Twenty-two female participants were separated into two groups, including HIIT group who receive intervention and control group who did not receive the intervention. Each of the participants was interviewed to collect and record their medical history, and medical parameters including cardio-ankle vascular index (CAVI), flow-mediated dilation (FMD), and maximal oxygen consumption (VO2max) were measured as a baseline pre-test. The intervention was a cycling-based HIIT lasting 6 weeks, with three sessions per week. During each session, the participant completed a set protocol consisting of 1 min on a cycle ergometer, cycling at 80-85% maximal heart rate, followed by a 1-min rest period. This sequence was repeated for a total of 5 times. RESULTS: After 6 weeks of intervention, results showed that the HIIT group had significant improvements in CAVI (6.39 ± 0.76 vs. 5.91 ± 0.58), FMD (9.26 ± 6.5 vs. 14.01 ± 4.3%), and VO2max (20.10 ± 4.31 vs. 24.34 ± 5.71 ml/kg/min) values compared to the pre-test (P < 0.05). In addition, HIIT increased endothelial function as measured by FMD compared to the control group (14.01 ± 4.3 vs. 9.15 ± 4.16 %, P < 0.05). CONCLUSION: Six weeks of HIIT were found to improve vascular function and cardiorespiratory fitness in sedentary people and demonstrated the benefits of HIIT as a time-efficient exercise strategy.

Prehypertension and high serum uric acid increase risk of arterial stiffness.

Prehypertension and serum uric acid are emerging as independent risk factors for arterial stiffness and may also predict cardiovascular diseases. Previous studies have demonstrated the association between serum uric acid and arterial stiffness in hypertensive adults, but there are limited studies in prehypertensive adults. We compared the serum uric acid (SUA) and cardio-ankle vascular index (CAVI) between normotensive and prehypertensive participants. The association between SUA, prehypertension and CAVI were investigated. One hundred and eighteen participants were recruited and divided into two groups according to their blood pressure (normotensive, 53 and prehypertensive, 65). Blood pressure, resting heart rate, pulsatile stress, height, waist circumference and body composition were measured. After an overnight fast, blood samples were collected to measure lipid profile and SUA levels. Arterial stiffness was assessed according to the CAVI. The results showed that the SUA and CAVI of the prehypertensive group were significantly higher than those of the normotensive group. Multiple regression analysis demonstrated that CAVI was significantly correlated with age, systolic blood pressure and SUA. Furthermore, prehypertension and high SUA were significantly associated with increased risk of abnormal CAVI (relative risk, 2.696; 95% CI, 1.552-4.683; p < .001). The study demonstrated that prehypertension and high SUA significantly increased the risk of arterial stiffness as assessed by CAVI.

Directed evolution of an angiopoietin-2 ligand trap by somatic hypermutation and cell surface display.

Tie2 is a receptor tyrosine kinase that is essential for the development and maintenance of blood vessels through binding the soluble ligands angiopoietin 1 (Ang1) and 2 (Ang2). Ang1 is constitutively produced by perivascular cells and is protective of the adult vasculature. Ang2 plays an important role in blood vessel formation and is normally expressed during development. However, its re-expression in disease states, including cancer and sepsis, results in destabilization of blood vessels contributing to the pathology of these conditions. Ang2 is thus an attractive therapeutic target. Here we report the directed evolution of a ligand trap for Ang2 by harnessing the B cell somatic hypermutation machinery and coupling this to selectable cell surface display of a Tie2 ectodomain. Directed evolution produced an unexpected combination of mutations resulting in loss of Ang1 binding but maintenance of Ang2 binding. A soluble form of the evolved ectodomain binds Ang2 but not Ang1. Furthermore, the soluble evolved ectodomain blocks Ang2 effects on endothelial cells without interfering with Ang1 activity. Our study has created a novel Ang2 ligand trap and provided proof of concept for combining surface display and exogenous gene diversification in B cells for evolution of a non-immunoglobulin target.