A Novel Methodology for Semi-automatic Measurement of Arterial Stiffness by Doppler Ultrasound: Clinical Feasibility and Reproducibility.

The conventional manual approach to measurement of aortic pulse wave velocity (PWV) by Doppler ultrasonography is time consuming and operator dependent. Here we report a new semi-automated methodology for more efficient and objective measurement of aortic PWV and results of tests of its clinical feasibility and reproducibility. Carotid-femoral pulse wave velocity (cfPWV) was measured in 50 patients with suspected coronary artery disease (aged 59.2 ± 10.0 y, 36 males) by three independent observers, including two experienced sonographers and one cardiologist without ultrasonographic experience. The cfPWV measured by the semi-automatic method (cfPWVA) was compared with reference values obtained by averaging measurements by two experienced sonographers using the conventional standard manual method (cfPWVM). Measurements of cfPWVA were feasible in all 50 patients and exhibited excellent agreement with averaged cfPWVM from the two experienced sonographers, with an intraclass correlation coefficient (ICC) of 0.915 (95% confidence interval: 0.876-0.942). The inexperienced observer-measured cfPWVA did not differ from the cfPWVM measured by the two experienced sonographers (8.04 ± 1.29 vs. 8.14 ± 1.32 m/s, p > 0.05), with a high consistency by ICC of 0.877 (0.793-0.928). Bland-Altman plots further illustrated the good agreement between the two methods and good intra- and inter-observer reproducibility. Time consumption for cfPWV measurement using the new method was significantly less than that for the manual method (122 ± 35 s vs. 455 ± 105 s, p < 0.0001), saving about 73% of the time. This new semi-automatic methodology for aortic PWV measurement not only has an accuracy similar to that of the conventional standard manual method but is also highly feasible and time saving. It may provide a reliable, simple and reproducible approach to arterial stiffness evaluation in clinical settings.

Upregulation of iASPP ameliorates hypoxia/reoxygenation-induced apoptosis and oxidative stress in cardiomyocytes by upregulating Nrf2 signaling.

The inhibitor of apoptosis-stimulating protein of p53 (iASPP) acts as a key modulator of cellular protection against oxidative stress. In the present work, we assessed the role of iASPP in the regulation of cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). We found that H/R-exposed cardiomyocytes expressed decreased levels of iASPP. The upregulation of iASPP repressed H/R-induced injury by decreasing levels of apoptosis and reactive oxygen species production. The upregulation of iASPP increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and enhanced Nrf2 activation. The overexpression of Kelch-like ECH-associated protein 1 reversed iASPP-mediated promotion of Nrf2 activation. Nrf2 inhibition abrogated iASPP-mediated cardioprotective effects in H/R-exposed cardiomyocytes. Our work demonstrates that the upregulation of iASPP ameliorates H/R-induced apoptosis and oxidative stress in cardiomyocytes via potentiating Nrf2 signaling via modulation of Keap1.

Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1-p53 activation.

BACKGROUND: Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. METHODS: HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. RESULTS: Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. CONCLUSION: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1-p53 pathway.