RESCUE BT Trial Investigators E ndovascular treatment has been shown to significantly increase the reperfusion rate and improve the functional outcomes of patients with acute ischemic stroke due to large vessel occlusion. [1][2][3][4] However, endovascular thrombectomy has historically failed to yield successful reperfusion in approximately 30% of patients. 5 Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications. 6,7 Tirofiban, a highly selective nonpeptide platelet glycoprotein IIb/IIIa inhibitor with a relatively short half-life that can reversibly prevent platelet aggregation, has been proven to reduce the risk of thrombotic complications during percutaneous coronary intervention. [8][9][10] Given the benefit of treatment of acute coronary syndromes, a growing number of studies have evaluated tirofiban as an adjunctive treatment in patients with large vessel occlusion ischemic stroke IMPORTANCE Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.OBJECTIVE To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well.

Xian Fu and Chuming Huang contributed equally to this work Aim: Pulse wave velocity (PWV) has been regarded as the "gold standard" measurement of arterial stiffness (AS), but it is still only used in the assessment of central and peripheral arteries. We constructed a new method to evaluate cerebral AS by measuring PWV using transcranial Doppler (TCD). Methods: In all, 90 healthy subjects who received annual health screening were consecutively enrolled in this study between January 2011 and June 2013. Data on clinical characteristics, brachium-ankle (ba) PWV, and carotid-cerebral (cc) PWV measured with our newly constructed method by two experienced operators were recorded. cc PWV was calculated as the distance between two points in the common carotid artery and proximal part of ipsilateral middle cerebral artery, which was divided by the pulse transit time between these two points where the pulse was measured using TCD. Results: The value of cc PWV was 499.3 78.6 cm/s. Correlation between cc PWV and ba PWV in the assessment of AS was r 0.794 (P 0.001). The concordance between both the above mentioned methods was good. Interobserver and intraobserver reliability using interclass correlation for measuring cc PWV were 0.815 (P 0.001) and 0.939 (P 0.001), respectively. In multivariable analysis, older age ( 4.51, P 0.001) and increased diastolic blood pressure ( 2.39, P 0.001) were independently associated with higher cc PWV. Conclusion: cc PWV measured using TCD may be a promising method for the assessment of human cerebral AS, which is independently associated with age and diastolic blood pressure.

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High density lipoprotein (HDL) has been proposed to be internalized and to promote reverse cholesterol transport in endothelial cells (ECs). However, the mechanism underlying these processes has not been studied. In this study, we aim to characterize HDL internalization and cholesterol efflux in ECs and regulatory mechanisms. We found mature HDL particles were reduced in patients with coronary artery disease (CAD), which was associated with an increase in CC-chemokine ligand 2 (CCL2). In cultured primary human coronary artery endothelial cells and human umbilical vein endothelial cells, we determined that CCL2 suppressed the binding (4 °C) and association (37 °C) of HDL to/with ECs and HDL cellular internalization. Furthermore, CCL2 inhibited [3H]cholesterol efflux to HDL/apoA1 in ECs. We further found that CCL2 induced CC-chemokine receptor 2 (CCR2) expression and siRNA-CCR2 reversed CCL2 suppression on HDL binding, association, internalization, and on cholesterol efflux in ECs. Moreover, CCL2 induced p42/44 mitogen-activated protein kinase (MAPK) phosphorylation via CCR2, and p42/44 MAPK inhibition reversed the suppression of CCL2 on HDL metabolism in ECs. Our study suggests that CCL2 was elevated in CAD patients. CCL2 suppressed HDL internalization and cholesterol efflux via CCR2 induction and p42/44 MAPK activation in ECs. CCL2 induction may contribute to impair HDL function and form atherosclerosis in CAD.