LncRNA XIST knockdown ameliorates oxidative low-density lipoprotein-induced endothelial cells injury by targeting miR-204-5p/TLR4

Oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury is a key contributor toatherosclerosis development. However, the role and mechanism of long noncoding RNA X-inactive specifictranscript (XIST) in atherosclerosis remain largely unknown. The ox-LDL-induced human umbilical veinendothelial cells (HUVECs) injury was analyzed by cell viability, apoptosis, inflammatory cytokines secretionand oxidative stress. The expression levels of XIST, microRNA-204-5p (miR-204-5p) and toll-like receptor 4(TLR4) were detected by quantitative real-time polymerase chain reaction and western blot, respectively. Thetarget interaction between miR-204-5p and XIST or TLR4 was explored by bioinformatics analysis, luciferaseassay and RNA immunoprecipitation. The expression of XIST was enhanced in ox-LDL-treatedHUVECs. Knockdown of XIST attenuated ox-LDL-induced viability inhibition, apoptosis production,inflammatory response and oxidative stress in HUVECs. XIST was validated as a sponge of miR-204-5pand TLR4 acted as a target of miR-204-5p. Knockdown of miR-204-5p reversed silence of XISTmediated suppressive role in ox-LDL-induced injury. TLR4 alleviated miR-204-5p-mediated inhibitiveeffect on ox-LDL-induced injury. Moreover, XIST could regulate TLR4 expression by spongingmiR-204-5p. In conclusion, silence of XIST displayed a protective role in ox-LDL-induced injury inHUVECs by regulating miR-204-5p/TLR4 axis, providing a novel mechanism for understanding thepathogenesis of atherosclerosis.

Evaluation of volume responsiveness by pulse pressure variability and inferior vena cava dispensability index at different tidal volumes by mechanical ventilation

This study investigated the effects of tidal volume (TV) on the diagnostic value of pulse pressure variation (PPV) and the inferior vena cava dispensability index (IVC-DI) for volume responsiveness during mechanical ventilation. In patients undergoing elective surgery with mechanical ventilation, different TVs of 6, 9, and 12 mL/kg were given for two min. The left ventricular outflow tract velocity-time integral (VTI) was measured by transthoracic echocardiography. The IVC-DI was measured at sub-xyphoid transabdominal long axis. The PPV was measured via the radial artery and served as baseline. Index measurements were repeated after fluid challenge. VTI increased by more than 15% after fluid challenge, which was considered as volume responsive. Seventy-nine patients were enrolled, 38 of whom were considered positive volume responsive. Baseline data between the response group and the non-response group were similar. Receiver operating characteristic curve confirmed PPV accuracy in diagnosing an increase in volume responsiveness with increased TV. When TV was 12 mL/kg, the PPV area under the curve (AUC) was 0.93 and the threshold value was 15.5%. IVC-DI had the highest diagnostic accuracy at a TV of 9 mL/kg and an AUC of 0.79, with a threshold value of 15.3%. When TV increased to 12 mL/kg, the IVC-DI value decreased. When the TV was 9 and 12 mL/kg, PPV showed improved performance in diagnosing volume responsiveness than did IVC-DI. PPV diagnostic accuracy in mechanically ventilated patients was higher than IVC-DI. PPV accuracy in predicting volume responsiveness was increased by increasing TV.