The physiological role of autophagic flux within the vascular endothelial layer remains poorly understood. Here, we show that in primary endothelial cells, oxidized and native LDL stimulates autophagosome formation. Moreover, by both confocal and electron microscopy, excess native or modified LDL appears to be engulfed within autophagic structures. Transient knockdown of the essential autophagy gene ATG7 resulted in higher levels of intracellular (125) I-LDL and oxidized LDL (OxLDL) accumulation, suggesting that in endothelial cells, autophagy may represent an important mechanism to regulate excess, exogenous lipids. The physiological importance of these observations was assessed using mice containing a conditional deletion of ATG7 within the endothelium. Following acute intravenous infusion of fluorescently labeled OxLDL, mice lacking endothelial expression of ATG7 demonstrated prolonged retention of OxLDL within the retinal pigment epithelium (RPE) and choroidal endothelium of the eye. In a chronic model of lipid excess, we analyzed atherosclerotic burden in ApoE(-/-) mice with or without endothelial autophagic flux. The absence of endothelial autophagy markedly increased atherosclerotic burden. Thus, in both an acute and chronic in vivo model, endothelial autophagy appears critically important in limiting lipid accumulation within the vessel wall. As such, strategies that stimulate autophagy, or prevent the age-dependent decline in autophagic flux, might be particularly beneficial in treating atherosclerotic vascular disease.

Pulmonary fibrosis is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix components. Although the origin of fibroblasts is multifactorial, recent data implicate endothelial-to-mesenchymal transition as an important source of fibroblasts. We report herein that loss of the essential autophagy gene ATG7 in endothelial cells (ECs) leads to impaired autophagic flux accompanied by marked changes in EC architecture, loss of endothelial, and gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition. Loss of ATG7 also up-regulates TGFβ signaling and key pro-fibrotic genes in vitro. In vivo, EC-specific ATG7 knock-out mice exhibit a basal reduction in endothelial-specific markers and demonstrate an increased susceptibility to bleomycin-induced pulmonary fibrosis and collagen accumulation. Our findings help define the role of endothelial autophagy as a potential therapeutic target to limit organ fibrosis, a condition for which presently there are no effective available treatments.

Background: Medical students encounter various stressors during their studies. The study aimed to assess stress levels, sources, and associated determinants among Sudanese medical students. Method: An online questionnaire-based study was conducted among 617 undergraduate medical students of 6 different universities in Sudan. A 19-item questionnaire was utilized to assess stress sources, in addition to demographics, stress manifestations, and coping strategies. Results: The overall prevalence of stress was 31.7% (p < 0.05). The main sources of stress were time pressure, heavy workload, fear of failure, and examination frequency. One-third of students indicated that they experienced at least one source of psychosocial- and teaching-related stress. Female medical students were more significantly stressed due to academics than males. Also, fourth- and fifth-year students were academically more stressed in comparison to the first-year students. Poisson regression analysis model showed that first-year students were less stressed than the final-year students in relation to academics (odds = 0.888, P = 0.003). Male medical students, across all study years, were far less stressed than females (odds = 0.901, P = 0.000153). Expectedly, ‘studying medicine by choice’ was associated with decreased odds for psychosocial stressors (odds = 0.885, P = 0.00781), and improved model-fit (chi-squared = 6.8952, P = 0.008643). Also, the year of study was a predictor of teaching-related stress development. Conclusions: Female medical students were more stressed due to academics than males. On the other hand, final-year students were more academically stressed than first-year students. Female medical students were likely having stress related to academic stress development, while being first-year medical student was a predictor of not developing academic stress. Studying medicine by choice’ was associated with ability to cope against stress.