Abnormal nonstoring capillary endothelium: a novel feature of Gaucher disease. Ultrastructural study of dermal capillaries

Abstract

Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD) patients (types II and III) revealed hitherto unknown alteration of the blood capillary endothelial cells (ECs) featured by hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes. There was also prominent apical membrane folding with formation of filiform and large cytoplasmic projections, with occasional transcapillary cytoplasmic bridges. Similar, though less frequently expressed, changes were manifested at the basal membrane by numerous cytoplasmic projections into the subendothelial space. Regressive changes with EC breakdown were rare. Lysosomal storage was always absent. Besides EC hypertrophy, there was also increased EC density in the capillary lumen, leading to pronounced changes in capillary architecture with loose or incomplete EC anchoring. There were also signs of EC sprouting. Some pericytes displayed an increase in size and number of cytoplasmic processes, which often extended into distant pericapillary regions. The spectrum of changes suggests that a significant positive growth effect on EC occurs in GD. The putative mechanisms triggered by GBA1 deficiency leading to EC involvement are discussed. The authors are well aware of the fact the results, based on a nontraditional type of bioptic samples, are preliminary, but they are worth following, as further ultrastructural and functional studies of blood endothelium in GD may open a novel field in molecular cell pathophysiology of the disorder: endothelial dysfunction.

Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease

“…Besides GLD, brain alterations of the microvascular angioarchitecture may occur also in adrenoleukostrophy, Canavan's disease and Alexander's disease patients [38,39]. Of note, b-glucosylpsychosine (1-b-D-glucosylsphingosine) purified from human Gaucher spleen exerts an inhibitory effect on endothelial cell proliferation and motility similar to psychosine [11], and ultrastructural abnormalities occur in capillary endothelial cells in skin biopsies from patients with acute neuronopathic infantile Gaucher disease [40]. Together, these observations point to endothelial dysfunction as a common factor in severe lysosomal diseases.…”

Unfavorable hip stress distribution after Legg–Calvé–Perthes syndrome: A 25‐year follow‐up of 135 hips

“…Avascular necrosis has also been connected to corticosteroid therapy, trauma, arterial disease, connective tissue disease (rheumatoid arthritis and systemic lupus erythematosus), sickle cell disease, alcoholism, Gaucher's disease, disseminated intravascular coagulation, intraosseous malignancy (especially lymphoma), and HIV . A common feature of these conditions is an increased concentration of microvesicles in isolates from peripheral blood . Platelet‐derived microvesicles carry tissue factor and may expose negatively charged phosphatidylserine on their exterior, so they are prothrombogenic and may cause formation of clots in blood vessels .…”

Gaucher disease geneGBAfunctions in immune regulation

“…Increasing clinical evidence suggests that the pathophysiology of classic GD is more complex and involves system-wide dysfunction of cell types other than macrophages (3)(4)(5). The involvement of immune cells has been implicated, but the underlying molecular defect is poorly understood (6)(7)(8)(9).…”