Pulmonary hypertension in sickle cell disease is an independent predictor of mortality, yet the pathogenesis of pulmonary vascular disease in chronic hemolytic disorders remains incompletely understood and treatment options are limited primarily to supportive care. The release of extracellular hemoglobin has been implicated in the development of pulmonary hypertension, and in this study we explored the direct effects of hemin, the oxidized moiety of heme, on the pulmonary artery endothelium. We found that low dose hemin exposure leads to significantly increased endothelial cell proliferation, migration, and cytokine release as markers of endothelial dysfunction. Protein expression changes in our pulmonary artery endothelial cells showed upregulation of mesenchymal markers after hemin treatment in conjunction with a decrease in endothelial markers. Endothelial to mesenchymal transition (EndoMT) resulting from hemin exposure was further confirmed by showing upregulation of the transcription factors SNAI1 and SLUG, known to regulate EndoMT. Lastly, given the endothelial dysfunction and phenotypic transition observed, the endothelial cytoskeleton was considered a potential novel target. Inhibiting myosin light chain kinase, to prevent phosphorylation of myosin light chain and cytoskeletal contraction, attenuated hemin-induced endothelial hyper-proliferation, migration, and cytokine release. The findings in this study implicate hemin as a key inducer of endothelial dysfunction through EndoMT, which may play an important role in pulmonary vascular remodeling during the development of pulmonary hypertension in chronic hemolytic states.
Background The popularity of short-term global health experiences amongst US medical students has been increasing. However, it remains a challenge for medical schools to comprehensively prepare students to work in an international environment and to contribute in ethically responsible and meaningful ways. Students of the Global Medicine program (GMED) of the UIC College of Medicine Center for Global Health set out to develop a pre-and-post travel curriculum that addresses some of these challenges. Methods The students surveyed the literature and published global health curricula and identified aspects of pre-and-post travel training that were found to be under-addressed in the. They then developed a curriculum in conjunction with GMED faculty that incorporated these identified aspects of pre-and-post travel training. Results Five aspects of pre-and-post travel training were identified as being both under-addressed in the literature and in student’s personal experiences while traveling. These domains include: (1) examining power relations associated with neo-colonization between and within countries; (2) training for bi-directional learning; (3) examining motivations and goals for participating in global health; (4) addressing personal resiliency and psychosocial wellbeing related to students’ travel, and; (5) reflecting on the challenging aspects of the fieldwork experience. Conclusions The student-driven curriculum is being integrated into the GMED program through structured didactic sessions, one-on-one mentor meetings and small group discussions. Once students have traveled, an evaluation of the curriculum will be conducted together with the foreign partners they visited.
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