Annular vasculitic lesions.

Vasculitic skin findings may present with annular morphologies. This group of conditions consists of capillaritis, such as pigmented purpuric dermatoses, and vasculitis, which is often classified by the affected vessel size. Annular vasculitic lesions may be the presenting sign of systemic disease, thus requiring thorough exploration to reach an accurate diagnosis and guide proper disease management. Herein we review the clinical presentation, histopathology, and treatments for cutaneous vasculitic disease that may present with annular lesions.

Hypoxia Stimulates Synthesis of Neutrophil Gelatinase-Associated Lipocalin in Aortic Valve Disease.

Objective: Aortic valve disease is commonly found in the elderly population. It is characterized by dysregulated extracellular matrix remodeling followed by extensive microcalcification of the aortic valve and activation of valve interstitial cells. The mechanism behind these events are largely unknown. Studies have reported expression of hypoxia inducible factor-1 alpha (HIF1α) in calcific nodules in aortic valve disease, therefore we investigated the effect of hypoxia on extracellular matrix remodeling in aged aortic valves. Approach and Results: Western blotting revealed elevated expression of HIF1α and the complex of matrix metalloprotease 9 (MMP9) and neutrophil gelatinase-associated lipocalin (NGAL) in aged porcine aortic valves cultured under hypoxic conditions. Consistently, immunofluorescence staining showed co-expression of MMP9 and NGAL in the fibrosa layer of these porcine hypoxic aortic valves. Gelatinase zymography demonstrated that the activity of MMP9-NGAL complex was significantly increased in aortic valves in 13% O2 compared to 20% O2. Importantly, the presence of ectopic elastic fibers in the fibrosa of hypoxic aortic valves, also detected in human diseased aortic valves, suggests altered elastin homeostasis due to hypoxia. Conclusion: This study demonstrates that hypoxia stimulates pathological extracellular matrix remodeling via expression of NGAL and MMP9 by valve interstitial cells.