Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation.

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow's direction on the blood vessel's luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.

Accuracy and Prognosis Value of the Sequential Organ Failure Assessment Score Combined With C-Reactive Protein in Patients With Complicated Infective Endocarditis.

This study aimed to evaluate the accuracy and prognostic value of the sequential organ failure assessment (SOFA) score combined with C-reactive protein (CRP) in patients with complicated infective endocarditis (IE). A total of 246 consecutive patients with complicated IE were included in the multicentric prospective observational study. These patients were divided into four groups depending on the SOFA score and CRP optimal cutoff values (≥5 points and ≥17.6 mg/L, respectively), which were determined using the receiver operating characteristic analysis: low SOFA and low CRP (n = 83), low SOFA and high CRP (n = 87), high SOFA and low CRP (n = 25), and high SOFA and high CRP (n = 51). The primary endpoint was in-hospital death, and the secondary endpoint was long-time mortality, defined as subsequent readmission and 3-years mortality in the follow-up period. High SOFA score and high CRP were associated with approximately 29.410% (15/51) of higher incidence of in-hospital death with an area under the curve of 0.872. Multivariate analyses showed that age [odds ratio (OR) = 2.242, 1.142-4.401], neurological failure (Glasgow Coma Scale ≤ 12) (OR = 2.513, 1.041-4.224), Staphylococcus aureus (OR = 2.151, 1.252-4.513), SOFA ≥ 5 (OR = 9.320, 3.621-16.847), and surgical treatment (OR = 0.121, 0.031-0.342) were clinical predictors for in-hospital death. On following up for 12-36 months, SOFA ≥ 5 (p = 0.000) showed higher mortality. A high SOFA score combined with increased CRP levels is associated with in-hospital mortality. Also, SOFA score, but not CRP, predicts long-term mortality in complicated IE.

Feasibility and Safety of the Distal Transradial Artery for Coronary Diagnostic or Interventional Catheterization.

BACKGROUND: This prospective study compared the success rate and safety of a distal transradial artery (dTRA) approach to that of the conventional transradial artery (TRA) for coronary angiography or percutaneous coronary intervention. METHODS: From January 2019 to April 2020, nine hundred consecutive patients (height < 190 cm) scheduled for coronary angiography or percutaneous coronary interventions were randomly and equally assigned to receive either dTRA or conventional TRA catheterization. RESULTS: Successful access was achieved in 96.00% and 96.67% of the dTRA and conventional TRA groups, respectively (P=0.814). Compared with the TRA group, patients in the dTRA experienced significantly less hemostatic band removal time (150.5 ± 50.5 cf. 210.6 ± 60.5 min, P=0.032); minor bleeding of the access site (2.44% cf. 6.44%, P=0.038); hemostatic band cost (USD; 0.1 cf. 59.4, P=0); and postprocedural radial artery occlusion (1.56% cf. 3.78%, P=0.035). A lower body mass index was a higher risk factor for dTRA access failure (odds ratio = 0.79, P=0.024), with a cutoff of 22.04 kg/m2. CONCLUSION: Compared to conventional TRA, dTRA had a comparable high success rate, with fewer associated complications. Clinicians should use the dTRA with caution in patients with low body mass index.

A comprehensive clinical diagnostic score system for prediction of coronary artery spasm in patients with acute chest pain.

BACKGROUND: Currently, there is no validated multivariate model to predict probability of coronary artery spasm (CAS) in patients with acute chest pain. METHODS: A total of 976 consecutive patients with acute chest pain were enrolled. Patients were divided into two groups based on the presence of significant CAS. To adjust potential confounders, a multivariable analysis was performed and a clinical diagnostic score system for CAS was utilized for score derivation. RESULTS: Multivariable analysis model selected 6 predictors for CAS. The integer score was assigned to each predictors: angina at rest alone (10 points), positive of hyperventilation test (8 points), allergies (3 points), asthma, ST-segment elevation and myocardial bridge (2 points each). We showed that the clinical diagnostic score system had accuracy in predicting CAS, as measured by the area under the curve (AUC), which was 0.952-0.966. The cut-off baseline value for the clinical diagnostic score system was set to 11-12 points with specificity of 91.0-93.3% and sensitivity of 90.7-92.9%, respectively. CONCLUSION: A clinical diagnostic score system was derived and validated as an accurate tool for estimating the pretest probability of CAS in patients with acute chest pain.

Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/ß-catenin pathway.

Atherosclerosis is the major cause of stroke and heart disease. However, the course and pathogenesis of atherosclerosis remains unknown. The proliferation and migration of endothelial cell play important roles in the inition and pathological progression of atherosclerosis. In this study, we demonstrated that long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression level was higher in coronary artery disease (CAD) tissues than in normal arterial tissues. The expression level of HOTTIP was upregulated in the proliferating endothelial cells induced by TNF-α or PDGF-BB. Ectopic expression of HOTTIP promoted endothelial cell proliferation and also increased the expression of proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP promoted endothelial cell migration. Downregulation expression of HOTTIP suppressed endothelial cell proliferation and migration. Furthermore, we determined that overexpression of HOTTIP induced ß-catenin expression and enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic expression of HOTTIP increased endothelial cell proliferation and migration via activation of the Wnt/ß-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/ß-catenin pathway.

Imperatorin protects H9c2 cardiomyoblasts cells from hypoxia/reoxygenation-induced injury through activation of ERK signaling pathway.

BACKGROUND: Imperatorin is a compound found in plants and has been widely used in Chinese medicine for many years. It has many pharmacological effects, including the recently reported anti-apoptotic function, however, the mechanism largely remains unclear. This study is aimed to elucidate the mechanism of Imperatorin's anti-apoptotic function. METHODS: A model of hypoxia and reoxygenation (H/R) treated h9c2 cardiomyoblasts was successfully constructed. The cells were treated with H/R condition, and followed by adding Imperatorin alone, Imperatorin with ERK inhibitor and/or ERK inhibitor alone, to examine the cell viability by Cell Counting Kit-8 assay, cell apoptosis rate by flow cytometry, and ERK expression by Western-blot under different conditions. RESULTS: The results showed that imperatorin exerted protective effect on h9c2 cells from H/R injure. It was also found that it not only increased cell viability but also reduced the apoptotic rate for H/R treated h9c2 cells. The experiments also demonstrated that imperatorin could upregulate the expression levels of both ERK1 and ERK2, which is a key step in ERK signaling pathway activation. CONCLUSIONS: These findings provided evidence that imperatorin could increase the cell viability and lower apoptotic rate in H/R treated h9c2 cells, and could also enhance the expression of ERK1/ERK2, demonstrating imperatorin's protective effect on H/R injured h9c2 cells through ERK signaling pathway.

Relationship of SELE A561C and G98T Variants With the Susceptibility to CAD.

Published genetic association studies have produced controversial results regarding the association of SELE gene polymorphisms (A516C and G98T) and CAD susceptibility. We therefore chose to perform a meta-analysis to determine the association.Twenty-seven eligible articles were identified through electronic databases, providing 5170 CAD cases and 4996 controls. Fixed-effects or random-effects summary ORs were calculated to estimate the risk of CAD in relation to A516C and G98T. Forest plots and funnel plots were constructed by Stata software 12.0.A strong association was observed between A516C and susceptibility of CAD among 4757 cases and 4272 controls. The summary OR was greatest in individuals carrying the CC genotype (OR = 1.91, 95% CI, 1.12-3.25). A significantly increased risk was indicated in both Caucasians and Asians. The analyses by disease type showed a significant increase in the risk of AP and MI. We also noted a strong association in population-based studies. In the analyses of G98T, data were available for 1422 cases and 1625 controls. We saw a markedly increased risk of CAD associated with G98T. The highest risk was indicated in individuals with the TT genotype (OR = 2.82, 95% CI, 1.15-6.89). A similar trend was seen in Asians and population-based studies.These findings provide consistent evidence that A516C and G98T polymorphisms of the SELE gene may be associated with increased susceptibility of CAD.