Microcirculation : the official journal of the Microcirculatory Society, Inc
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Therapeutic angiogenesis requires an understanding of how growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) result in physiological neovascularization. This study determined the physiological mechanism by which adenoviral delivery of growth factor combinations alter vascular phenotype and functionality. ⋯ Ang-1 and VEGF use different physiological mechanisms to enhance neovascularization of relatively avascular tissue. Administration of both growth factors combines these physiological mechanisms to give greater enhancement of neovascularization than either growth factor alone. These results suggest that effective revascularization therapy may require combination growth factor treatment.
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Comparative Study
Glucocorticoids inhibit the cerebral microvascular dysfunction associated with sepsis in obese mice.
Obesity is associated with increased morbidity and mortality in critically ill patients. It is unclear whether this increase is due to exaggerated inflammatory response alone or due to lack of response to therapeutic agents used. The objective of this study was to determine whether low-dose steroid therapy, which has proven effective in clinical setting, affords any benefit in the increased morbidity to sepsis in genetically obese (ob/ob) mice. ⋯ Low-dose glucocorticoid therapy is beneficial in experimental sepsis in obese animals compared to lean animals.
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Vascular endothelial growth factor (VEGF) plays an important role in the regulation of microvascular permeability under various physiological and pathological conditions. The authors tested the hypothesis that the small GTPase Rho and its downstream effector ROCK (Rho-associated coiled-coil-containing protein kinase) mediate VEGF-induced increases in venular permeability. They also investigated myosin light chain (MLC) phosphorylation and actin polymerization, two well-characterized targets of the Rho-ROCK pathway that are implicated in the regulation of endothelial barrier function. ⋯ Collectively, these findings suggest that the Rho-ROCK signal pathway contributes to VEGF-induced hyperpermeability. Myosin light-chain phosphorylation and actin stress fiber formation occur concomitantly with the increase in permeability upon VEGF stimulation.
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Sepsis is a major clinical problem that often results in the dysfunction or failure of multiple organs, including the liver. While inflammatory cell activation has been implicated as an early critical event in sepsis-induced liver dysfunction, there is growing evidence for the involvement of activated platelets in this pathologic process. ⋯ These findings indicate that sepsis is associated with a neutrophil-dependent recruitment of platelets in the liver microcirculation that impairs sinusoidal perfusion and may contribute to the liver dysfunction associated with sepsis.
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Comparative Study
Tissue bioenergetics and microvascular perfusion are impaired in rat ileal mucosa in normotensive sepsis.
Sepsis is a systemic inflammatory response to a bacterial infection. Inflammation may result in injury to the small bowel and an increase in translocation of bacteria and toxins across the mucosal barrier, which may contribute to the progression of sepsis. Microcirculatory perfusion or cytopathic hypoxia may cause impairment of tissue bioenergetics and injury in sepsis. The objective of this study was to determine if sepsis is associated with microcirculatory hypoperfusion and impaired tissue bioenergetics in the ileal mucosa. ⋯ Sepsis is associated with bioenergetic impairment and capillary hypoperfusion at the villus tip and a decrease in red cell flux in the central arteriole.