Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells.

BACKGROUND: Endothelial cell injury is a common nidus of renal injury in patients and consistent with the high prevalence of AKI reported during the coronavirus disease 2019 pandemic. This cell type expresses integrin α5 (ITGA5), which is essential to the Tie2 signaling pathway. The microRNA miR-218-5p is upregulated in endothelial progenitor cells (EPCs) after hypoxia, but microRNA regulation of Tie2 in the EPC lineage is unclear. METHODS: We isolated human kidney-derived EPCs (hkEPCs) and surveyed microRNA target transcripts. A preclinical model of ischemic kidney injury was used to evaluate the effect of hkEPCs on capillary repair. We used a genetic knockout model to evaluate the effect of deleting endogenous expression of miR-218 specifically in angioblasts. RESULTS: After ischemic in vitro preconditioning, miR-218-5p was elevated in hkEPCs. We found miR-218-5p bound to ITGA5 mRNA transcript and decreased ITGA5 protein expression. Phosphorylation of 42/44 MAPK decreased by 73.6% in hkEPCs treated with miR-218-5p. Cells supplemented with miR-218-5p downregulated ITGA5 synthesis and decreased 42/44 MAPK phosphorylation. In a CD309-Cre/miR-218-2-LoxP mammalian model (a conditional knockout mouse model designed to delete pre-miR-218-2 exclusively in CD309+ cells), homozygotes at e18.5 contained avascular glomeruli, whereas heterozygote adults showed susceptibility to kidney injury. Isolated EPCs from the mouse kidney contained high amounts of ITGA5 and showed decreased migratory capacity in three-dimensional cell culture. CONCLUSIONS: These results demonstrate the critical regulatory role of miR-218-5p in kidney EPC migration, a finding that may inform efforts to treat microvascular kidney injury via therapeutic cell delivery.

Alternative Diagnostic Strategy for the Assessment and Treatment of Pulmonary Embolus: A Case Series.

INTRODUCTION: Ferumoxytol-enhanced magnetic resonance angiography (FeMRA) can be used as an alternate and safe method to diagnose patients with compromised renal function who present with acute pulmonary embolus in the emergency department (ED) setting. CASE REPORT: A 62-year old man with a history of renal transplant and lymphoproliferative disease described new onset of breathlessness. His clinical symptoms were suggestive of pulmonary embolus. He underwent FeMRA in the ED to avoid exposure to intravenous iodinated contrast. FeMRA demonstrated a left main pulmonary artery embolus, which extended to the left interlobar pulmonary artery. Afterward, the patient initiated anticoagulation therapy. With preserved renal function he was able to continue his outpatient chemotherapy regimen. CONCLUSION: This case highlights a safe imaging technique for emergency physicians to diagnose pulmonary embolus and subsequently guide anticoagulation therapy for patients in whom use of conventional contrast is contraindicated.