Microvascular research
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Microvascular research · May 2008
Normal sublingual microcirculation during painful crisis in sickle cell disease.
Obstruction of the microcirculation is the most important cause of painful crisis in sickle cell disease (SCD). Extensive microvascular obstruction has been observed in mouse models of SCD. A technique to determine the extent of the microcirculatory obstructions in humans may be helpful in the clinical setting and for research purposes. ⋯ The mean MFI of patients with SCD during steady state (2.7+/-0.1) and the mean MFI of the controls (2.7+/-0.1) were not different from the mean MFI during painful crisis. During painful crisis irregular microvascular perfusion, expressed by the distribution width of the microvascular blood flow velocity, correlated negatively (r=-0.484; P=0.002) with hemoglobin concentration. We conclude that sublingual microcirculatory blood flow velocity is not disturbed in sickle cell patients during painful crisis.
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Microvascular research · May 2008
Impaired flow-mediated vasodilation in type 2 diabetes: lack of relation to microvascular dysfunction.
A reduced availability of nitric oxide (NO) is an important feature of endothelial dysfunction occurring early in the course of type 2 diabetes. The measurement of flow-mediated dilation (FMD) of the brachial artery after forearm ischemia is supposed to be a non-invasive method to assess endothelial production and release of NO. The impairment of reactive hyperemia due to microvascular dysfunction in diabetes might cause an insufficient increase in shear stress stimulating the endothelial NO release, thus leading to an underestimation of FMD. ⋯ FMD% was not related to CBV% (r=0.14; p=0.139). The lack of an association between the reduction of endothelium-dependent vasodilation of the brachial artery and the impairment of postocclusive microvascular hyperemia observed in the present study contradicts the assumption that a reduced FMD is only the consequence of an impaired reactive hyperemia due to microvascular dysfunction. It also lends support to the suggestion that endothelial dysfunction in conduit vessels and impaired cutaneous microvascular responses to reactive hyperemia might at least partly develop independently due to several differences in their pathogenesis.
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Microvascular research · Apr 2008
Heterogeneity of barrier function in the lung reflects diversity in endothelial cell junctions.
Endothelial cells assemble unique barriers that confer specific permeability requirements at different vascular segments. We examined lung microvascular and artery endothelial cells to gain insight into mechanisms for segment-specific barrier functions. Transendothelial electrical resistance was significantly higher in microvascular barriers, and a 50% reduction in barrier function required 5-fold higher concentration of cytochalasin D in the microvascular compared to the arterial barrier. ⋯ Confocal analysis revealed ALCAM in the lateral plasma membrane domain where it co-localized with N- and VE-cadherin. This finding was supported by co-immunoprecipitation studies demonstrating the presence of ALCAM in multiple adherens junction protein complexes. These functional, biophysical and molecular findings suggest specialization of the adherens junction as a basis for a highly restrictive endothelial barrier to control fluid flux into the alveolar airspace.
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Microvascular research · Jul 2007
Inducible NO synthase (iNOS) in human neutrophils but not pulmonary microvascular endothelial cells (PMVEC) mediates septic protein leak in vitro.
Sepsis-induced acute lung injury (ALI) is characterized by injury of the pulmonary microvascular endothelial cells (PMVEC) leading to high-protein pulmonary edema. Inducible NO synthase (iNOS) mediates trans-PMVEC protein leak in septic mice in vivo and in murine PMVEC under septic conditions in vitro, but the role of iNOS in human PMVEC protein leak has not been addressed. We hypothesized that iNOS in human neutrophils, but not human PMVEC, mediates septic trans-PMVEC protein leak in vitro. ⋯ Pre-treatment of neutrophil-PMVEC co-cultures with PEG-SOD (superoxide scavenger) and FeTPPS (peroxynitrite scavenger) also significantly attenuated neutrophil-dependent cytomix-stimulated leak (4.7+/-3.0%, p<0.05; 0.5+/-1.0%, p<0.01, respectively). In conclusion, trans-human PMVEC albumin leak under septic conditions is dependent on iNOS activity specifically in neutrophils, but not in PMVEC themselves. Septic neutrophil-dependent trans-PMVEC albumin leak may be mediated by peroxynitrite.
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Microvascular research · Mar 2006
Brief heat shock affects the permeability and thermotolerance of an in vitro blood-brain barrier model of porcine brain microvascular endothelial cells.
Heat shock was imposed on an in vitro model of the blood-brain barrier (BBB) by submersion into prewarmed growth medium. Transendothelial electrical resistance (TEER) was used to assess the functional integrity of the endothelial barrier. Consequences of the heat shock were highly dependent upon the temperature and duration of exposure. ⋯ The BBB models lost more than 60% of barrier function when initially exposed to 53 degrees C for 5 s but lost only 30% of function when exposed to the same treatment 24 h later. The BBB models over-compensated to produce a reinforced barrier with double the original TEER following repeated application of heat treatment (57 degrees C for 3 s). In vivo experiments will require exquisite manipulation of the temperature and duration in order to achieve the desired opening of the BBB in therapeutic applications.