BANP Participates in the Chronic Intermittent Hypoxia-Induced Senescence of Vascular Endothelial Cells by Promoting P53 Phosphorylation and Nuclear Retention.

INTRODUCTION: The objective of this study was to examine the potential induction of senescence in vascular endothelial cells (VECs) by chronic intermittent hypoxia (CIH), a defining characteristic of obstructive sleep apnea (OSA). This investigation seeks to elucidate the underlying mechanisms that contribute to the development of cardiovascular diseases in patients with OSA, with a particular focus on CIH-induced vascular aging. METHODS: The BioSpherix-OxyCycler system was used to establish models of CIH in both rats and human umbilical vein endothelial cells (HUVECs). To assess VECs' senescence, various methods were employed including EdU incorporation assay, cell cycle analysis, senescence-associated ß-galactosidase (SA-ß-gal) staining, and senescence protein testing. Vascular aging was evaluated through measurements of carotid-femoral pulse wave velocity, intima-media thickness, and Ki67 immunohistochemical staining. In order to identify the molecular mechanisms associated with CIH-induced senescence in VECs, a bioinformatics study was conducted utilizing the Gene Expression Omnibus database. RESULTS: Under conditions of CIH, HUVECs exhibited inhibited proliferation, arrested cell cycle, increased activity of SA-ß-gal, and elevated expression levels of p53 and p21 compared to HUVECs under normoxic conditions. Similarly, rats exposed to CIH displayed increased carotid-femoral pulse wave velocity, intima-media thickness, vascular permeability, and SA-ß-gal activity in VECs, along with decreased expression of arterial Ki67. BTG3-associated protein (BANP) was found to be highly expressed in CIH-induced VECs. Furthermore, the overexpression of BANP resulted in the senescence of VECs, along with elevated levels of p53 phosphorylation and nuclear localization. CONCLUSIONS: These findings demonstrate that CIH can induce VECs senescence and contribute to vascular aging. Additionally, BANP can induce VECs senescence by promoting p53 phosphorylation and nuclear retention. These discoveries offer novel insights into the increased cardiovascular risk associated with OSA, thereby presenting new possibilities for therapeutic intervention.

Soluble Vascular Cell Adhesion Molecule-1 as an Inflammation-Related Biomarker of Coronary Slow Flow.

Background: Coronary slow flow (CSF) is an angiographic entity characterized by delayed coronary opacification with no evident obstructive lesion in the epicardial coronary artery. Several studies have shown that the occurrence and development of CSF may be closely related to inflammation. Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker related to inflammation. The aim of this study was to evaluate the correlation between plasma soluble VCAM-1 level and CSF occurrence and thus the predictive value of VCAM-1 for CSF. Methods: Forty-six CSF patients and thirty control subjects were enrolled. Corrected thrombolysis in myocardial infarction frame count (cTFC) was used to diagnose CSF. Functional status and quality of life were determined by the Seattle Angina Questionnaire (SAQ). Echocardiography was used to evaluate the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV). The plasma levels of sVCAM-1, IL-6, and TNF-α were quantified by enzyme-linked immunosorbent assay. Results: Compared with the control group, the physical limitation score by the SAQ, the LV global longitudinal strain (GLS), mitral E, and mitral E/A decreased in patients with CSF, while the plasma IL-6 and TNF-α levels increased. The plasma sVCAM-1 level in the CSF group was significantly higher than that in the control group (186.03 ± 83.21 vs. 82.43 ± 42.12 ng/mL, p < 0.001), positively correlated with mean cTFC (r = 0.57, p < 0.001), and negatively correlated with the physical limitation score (r = −0.32, p = 0.004). Logistic regression analyses confirmed that plasma sVCAM-1 level (OR = 1.07, 95%CI: 1.03−1.11) is an independent predictor of CSF, and the receiver operating characteristic curve analysis showed that plasma sVCAM-1 levels had statistical significance in predicting CSF (area under curve = 0.88, p < 0.001). When the sVCAM-1 level was higher than 111.57 ng/mL, the sensitivity for predicting CSF was 87% and the specificity was 73%. Conclusions: Plasma sVCAM-1 level can be used to predict CSF and was associated with the clinical symptoms of patients. It may serve as a potential biomarker for CSF in the future.

Incremental Value of Three-dimensional Speckle-tracking Echocardiography for Evaluating Left Ventricular Systolic Function in Patients with Coronary Slow Flow.

The purpose was to evaluate left ventricular (LV) systolic function in patients with coronary slow flow (CSF), and compared the incremental values of 3-dimensional (3D) speckle-tracking echocardiography (STE). Seventy-three patients with CSF and 60 control subjects were enrolled. CSF was diagnosed during coronary angiography. Two-dimensional (2D) and 3D global strain were measured using STE. Sex, mitral E, 2D GLS, and all 3D strain parameters were independent predictors of CSF. Combination of sex, mitral E, and 3D GTS had the highest area under the curve (AUC) for identifying CSF (AUC, 0.81; P < 0.001). Integrated discrimination index (IDI) improved adding 3D GTS to the combined sex and mitral E model (IDI = 0.12, P = 0.01) or 2D GLS model (IDI = 0.14, P < 0.001). LV systolic function was impaired in CSF patients. 3D GTS had an independent and incremental value for predicting CSF compared with 2D echocardiography.

Incremental value of carotid elasticity modulus using shear wave elastography for identifying coronary artery disease in patients without carotid plaque.

BACKGROUND: Shear wave elastography (SWE) directly quantifies the local arterial wall stiffness by calculating the elastic modulus. However, whether carotid wall elastic modulus can predict obstructive coronary artery disease (CAD) is not well known. We aimed to investigate the value of carotid wall elastic modulus measured using SWE in identifying obstructive CAD. MATERIALS AND METHODS: We prospectively enrolled 61 patients without carotid plaque referred for clinically indicated coronary angiography. Twenty-seven (44.3%) patients were diagnosed with obstructive CAD (≥50% coronary stenosis). The elastic modulus of common carotid artery was quantified using SWE. Ankle--brachial index (ABI) and echocardiographic global cardiac calcium score (GCCS) were measured. RESULTS: Patients with obstructive CAD had significantly higher elastic modulus than those without obstructive CAD. The maximum elastic modulus (EMmax) was independently associated with obstructive CAD after adjusting for the Framingham risk score, ABI, and GCCS. EMmax had the highest area under the curve (AUC) to identify obstructive CAD (AUC 0.70; P = 0.003). In the nested models, the model based on the Framingham risk score and ABI (χ2 = 3.74) improved by adding GCCS (χ2 = 9.95) and further improved by adding EMmax (χ2 = 15.86). Adding EMmax to the combined ABI and GCCS model increased integrated discrimination index from 0.10 to 0.19. CONCLUSION: Carotid wall elastic modulus measured using SWE is a useful predictor of obstructive CAD in patients without carotid plaque. We demonstrated the incremental and independent value of carotid wall elastic modulus in identifying obstructive CAD compared with clinical risk factors and other imaging predictors, including ABI and GCCS. VIDEO ABSTRACT: Please see the video, in Supplemental Digital Content 1, http://links.lww.com/HJH/B551 for more insights from the authors.

Establishing normal reference value of carotid ultrafast pulse wave velocity and evaluating changes on coronary slow flow.

Pulse wave velocity (PWV) measured by ultrafast ultrasound imaging can early evaluate arteriosclerosis. The study aimed to establish normal reference range for ufPWV in healthy adults and explore its influencing factors, and evaluate the ufPWV changes on coronary slow flow (CSF). ufPWV at the beginning and end of systole (ufPWV-BS and ufPWV-ES, respectively) was measured in healthy adults (201 cases). CSF was diagnosed based on thrombolysis in myocardial infarction (TIMI) frame count during coronary angiography. ufPWV-BS and ufPWV-ES were compared between CSF (50 cases) and control groups (50 healthy age-, body mass index-, and blood pressure-matched adults). In healthy adults, average ufPWV-BS and ufPWV-ES was 5.36 ± 1.27 m/s and 6.99 ± 1.93 m/s, respectively. ufPWV-BS and ufPWV-ES positively correlated with age, body mass index, and blood pressure. ufPWV-BS and ufPWV-ES in the CSF group were higher than in the control group (ufPWV-BS, 6.05 ± 1.07 vs. 5.26 ± 0.89 m/s, P < 0.001; ufPWV-ES, 9.07 ± 1.84 vs. 6.84 ± 1.08 m/s, P < 0.001). Receiver operating characteristic curves showed that ufPWV-ES was more sensitive than ufPWV-BS. The normal reference range of ufPWV for healthy adults was established. Age, body mass index, and blood pressure were the main influencing factors. ufPWV was increased in the patients with CSF. The findings indicated that, in addition to reflecting atherosclerosis, ufPWV might also provide a basis for the noninvasive evaluation of microvascular impairment in the patients with CSF.

Value of exercise stress electrocardiography for stratification of exercise capacity and left ventricular systolic and diastolic function on coronary slow flow: case-control study.

BACKGROUND: Coronary slow flow phenomenon (CSFP) is an angiographic entity characterized by delayed coronary opacification in absence of evident obstructive lesion in the epicardial coronary artery. However, whether patients with CSFP exhibit differing responses to exercise is still not known. This study aimed to evaluate results of exercise stress electrocardiography (ExECG) and left ventricular (LV) function during exercise, and study the value of ExECG for stratification of exercise capacity and LV function in patients with CSFP. METHODS: Thirty patients with CSFP and 24 controls were enrolled in the study. Diagnosis of CSFP was made by Thrombolysis in Myocardial Infarction frame count. ExECG and LV function measured by echocardiography at rest, during exercise and recovery phase were evaluated. RESULTS: Negative ExECG was found in 24 (80%) patients with CSFP. At rest, LV global longitudinal strain (GLS) decreased and mitral average E/e' increased in patients with CSFP compared with controls; however, there were no differences in these parameters between CSFP patients with negative ExECG and patients with positive ExECG. During exercise, CSFP patients with negative ExECG and controls had significantly increased LV GLS and decreased mitral average E/e', but CSFP patients with positive ExECG had significantly decreased LV GLS and increased mitral average E/e'. CONCLUSIONS: About 80% patients with CSFP exhibited negative ExECG. CSFP patients with negative ExECG exhibited improved LV function but CSFP patients with positive ExECG exhibited impaired LV function during exercise. ExECG may aid in the stratification of exercise capacity and LV function in patients with CSFP.