Improving biological functions of endothelial progenitor cells (EPCs) is beneficial to maintaining endothelium homeostasis and promoting vascular re-endothelialization. Because macroautophagy/ autophagy has been documented as a double-edged sword in cell functions, its effects on EPCs remain to be elucidated. This study was designed to explore the role and molecular mechanisms of store-operated calcium entry (SOCE)-activated autophagy in proliferation of EPCs under hypercholesterolemia. We employed oxidized low-density lipoprotein (ox-LDL) to mimic hypercholesterolemia in bone marrowderived EPCs from rat. Ox-LDL dose-dependently activated autophagy flux, while inhibiting EPC proliferation. Importantly, inhibition of autophagy either by silencing Atg7 or by 3-methyladenine treatment, further aggravated proliferative inhibition by ox-LDL, suggesting the protective effects of autophagy against ox-LDL. Interestingly, ox-LDL increased STIM1 expression and intracellular Ca 2C concentration. Either Ca 2C chelators or deficiency in STIM1 attenuated ox-LDL-induced autophagy activation, confirming the involvement of SOCE in the process. Furthermore, CAMKK2 (calcium/ calmodulin-dependent protein kinase kinase 2, b) activation and MTOR (mechanistic target of rapamycin [serine/threonine kinase]) deactivation were associated with autophagy modulation. Together, our results reveal a novel signaling pathway of SOCE-CAMKK2 in the regulation of autophagy and offer new insights into the important roles of autophagy in maintaining proliferation and promoting the survival capability of EPCs. This may be beneficial to improving EPC transplantation efficacy and enhancing vascular reendothelialization in patients with hypercholesterolemia.

ObjectiveThe purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males.MethodsA prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points.ResultsWithin 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude.ConclusionUpon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.

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Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID‐19). However, little is known about the effects of pre‐admission and/or in‐hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in‐hospital blood pressure (BP) control and COVID‐19–related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID‐19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre‐admission usage of renin‐angiotensin‐aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14‐0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13‐0.97, P = .043) or after (HR = 0.18, 95%CI 0.04‐0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID‐19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01‐0.83, P = .033) than non‐RAAS inhibitors users. We revealed that COVID‐19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID‐19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID‐19 patients with hypertension before and after admission.