Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/β2GPI/anti-β2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/β2GPI/anti-β2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/β2GPI/anti-β2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.

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<b><i>Introduction:</i></b> Stroke has become a major disease that threatens the global population’s health and is a major public health problem that needs to be solved in China. Therefore, it is essential to analyze the trend of the mortality of stroke and its epidemic characteristic of stroke death. <b><i>Methods:</i></b> Death cases of stroke were reported to the national death registry system by the medical staff of all medical institutions, and the population data every year were obtained from District or County’s Statistic Bureau in Chongqing. They were analyzed to calculate the mortality, age-standardized mortality rate by Chinese standardization population (ASMRC), age-specific mortality, proportion, and annual percent of change (APC) according to the ICD-10 code. ASMRC was based on the standard population of the 6th census in China, 2010. The stroke mortality of each subgroup was compared using the χ² test. Trend analysis was presented by APC. <b><i>Results:</i></b> The crude mortality of stroke increased from 96.29 per 100,000 in 2012 to 115.93 per 100,000 significantly, with the APC of 2.02% (<i>t</i> = 2.82, <i>p</i> = 0.022) in Chongqing. ASMRC of stroke was 56.47 per 100,000 in 2012 and 54.70 per 100,000 in 2021, and its trend change was stable (APC = −0.01, <i>t</i> = 0.07, <i>p</i> = 0.947). The crude mortality of stroke in males was higher than that in females every year (<i>p</i> &lt; 0.05). The death proportion of intracerebral hemorrhage dwindled from 60.53% in 2012 to 49.88% in 2021, whereas the death proportion of ischemic stroke increased from 20.92% in 2012 to 39.96% in 2021. The average age of stroke death was delayed from 73.43 years old in 2012 to 76.52 years old in 2021 significantly (<i>t</i> = 18.12, <i>p</i> &lt; 0.001). The percentage of stroke death at home increased from 75.23% in 2012 to 79.23% in 2021, while the percentage of stroke death at hospitals decreased from 17.89% in 2012 to 15.89% in 2021. <b><i>Conclusion:</i></b> The crude mortality of stroke surged, and intracerebral hemorrhage was the main death cause of all subtypes. The mortality of stroke in males and rural residents was higher than that in females and urban residents. Most stroke deaths occurred at home. Male and rural residents were crucial populations for stroke prevention and control. There should be improved medical resources in rural areas and enhanced capability of stroke diagnosis and treatment.