OBJECTIVETo investigate the effect of low shear stress (LSS) on apoptosis of human vascular endothelial cells (ECs) and explore the possible mechanisms.

METHODSParallel flow chamber was used to apply LSS at 2 dyne/cm(2) on EA.hy926 cells derived from human umbilical vein endothelial cells for 120 min. Cell apoptosis following LSS was verified by morphological observation, DAPI staining and TUNEL test. The level of intracellular reactive oxygen species (ROS) was measured by dihydroethidium (DHE) and mitoSOX. Western blotting was performed to detect the activity of Akt in the cells.

RESULTSEC detachment and apoptosis were observed after exposure to 2 dyne/cm(2) LSS for 120 min. Time course study showed that the phosphorylation level of Akt on residues Ser473 and Thr308 was elevated after flow initiation. Exposure to LSS at 2 dyne/cm(2) for 120 min resulted in increased ROS production in the ECs at both the mitochondrial and cytoplasmic levels.

CONCLUSIONAkt activation and increased ROS levels are involved in LSS-induced EC apoptosis.

Apoptosis ; Cells, Cultured ; Endothelial Cells ; metabolism ; Endothelium, Vascular ; cytology ; Humans ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Stress, Mechanical

Objective:To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation.Methods:Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization.Results:ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions:This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.