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INTRODUCTION: Tumors that invade or compress the venous sinuses have the potential to impair venous drainage. Rarely, this may be so severe as to induce intracranial hypertension. Other studies have previously described venous sinus stenting (VSS) for the treatment of these symptomatic lesions. In this report, we present our series of eight cases of VSS for symptomatic tumor-induced venous sinus stenosis and review the existing literature. CASES: Eight patients with mostly intracranial tumors were found to have symptomatic venous sinus stenosis with the most common presenting symptom being elevated intracranial pressure. Six of the eight (75%) patients presented with papilledema on neuro-ophthalmological exam. The most affected locations were the transverse and sigmoid sinuses in four patients, followed by the superior sagittal sinus in three patients. All eight patients underwent VSS with no adverse events. In total, 6 out of 8 (75%) of patients had complete resolution of their symptoms, while the remaining patients experienced at least partial improvement. CONCLUSION: Tumors that cause symptomatic venous sinus stenosis may be successfully managed with VSS to improve venous drainage. This may facilitate continued conservative management of meningiomas or allow for treatment with noninvasive means, such as stereotactic radiosurgery. Depending on the size of the target stenosis, balloon-mounted coronary stents may be a suitable option to treat these lesions.
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BACKGROUND: Diabetic patients are at increased risk of complications from severe peripheral arterial disease. Mesenchymal stem cells (MSC) may be useful in limiting these complications. Our objective is to test the angiogenic potential of diabetic versus healthy MSCs. METHODS: MSCs' angiogenic potential was tested by endothelial cell (EC) proliferation, migration, and 3-dimensional sprouting. Diabetic conditions were simulated with 5.5, 20, or 40 mM glucose. MSC secretome was quantified by enzyme-linked immunosorbent assay. RESULTS: Human aortic ECs were most sensitive to glucose conditions and were used for all MSC experiments. Diabetic MSCs had greater 3-dimensional invasion than healthy MSCs (P<.05), but EC sprouting was decreased in high glucose conditions in both diabetic and healthy MSCs. Secretome analysis demonstrated that 20mM glucose stimulated epidermal growth factor (EGF) expression in diabetic and healthy MSCs, but that diabetic MSCs had a unique secretome with increased levels of chemokine (C-X-C motif) ligand 1 (CXCL-1), interleukin six (IL-6), and monocyte chemoattractant protein 1 (MCP-1) (P<.05). CONCLUSION: Despite having similar in vitro angiogenic activity, diabetic MSCs secrete a unique and inflammatory angiogenic signature that may influence MSC survival and function after transplantation in cell therapy applications. Strategies that normalize secretome in diabetic patients may improve the utility of autologous MSCs in this population of patients.
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Diabetes Mellitus/metabolismo , Células Endoteliales/fisiología , Células Madre Mesenquimatosas/metabolismo , Neovascularización Fisiológica/fisiología , Enfermedad Arterial Periférica/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Ensayo de Inmunoadsorción Enzimática , Humanos , Trasplante de Células Madre MesenquimatosasRESUMEN
BACKGROUND: Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries. METHODS: D-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared with unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow were tested ex vivo to validate critical results from the animal model. RESULTS: D-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified transforming growth factor-ß pathways as having a prominent role in this stiffened arterial response, but this was attributable to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to transforming growth factor-ß. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of transforming growth factor-ß in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild-type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model. CONCLUSIONS: TSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1's activation of the profibrotic signaling pathways of transforming growth factor-ß. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow.