D Granger

..These findings implicate leukocyte-associated AT(1)r and gp91(phox) in the induction of the pro-oxidative, proinflammatory, and prothrombogenic phenotype assumed by microvessels that is chronically exposed to elevated Ang II...

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..Future efforts to develop therapies that prevent the harmful effects of risk factor-induced inflammation should focus on the microcirculation...

..These factors also hold the promise of offering multiple sites for therapeutic intervention in CVD...

..These genes are relevant to the neuroprotection, regeneration and angiogenesis previously described following stem cell therapy in animal models of ischemic stroke...

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..Platelet- and endothelial cell-associated COX-1 promote microvascular inflammation and thrombogenesis during hypercholesterolemia, yet nitric oxide-releasing aspirin directly inhibits platelets independent of COX-1...

..These findings indicate that betaS mice assume both an inflammatory and prothrombogenic phenotype, with endothelial cell P-selectin playing a major role in mediating these microvascular responses...

..The authors examined the inflammatory and thrombogenic responses of the cerebral microvasculature to sepsis induced by cecal ligation and perforation in obese and lean wild-type mice...

..Both P-selectin and ICAM-1 contribute to the inflammatory and prothrombogenic state induced by cerebral I/R...

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..We propose that AT1-R engagement contributes to the prothrombogenic and proinflammatory state induced in venules by hypercholesterolemia...

..Our findings indicate that colonic inflammation is associated with the induction of a prothrombogenic phenotype in the colonic microcirculation, with P-selectin and its ligand PSGL-1 playing a major role in the recruitment of platelets...

..The objective of this study was to determine the relative contributions of blood cell-associated versus endothelium-associated AT1a-R to these hypercholesterolemia-induced microvascular alterations...

..Agents that act to maintain the normal balance between NO and reactive oxygen species (ROS) in vascular endothelial cells may prove particularly useful in this regard...

..The objective of this study was to define the contribution of T-lymphocyte-derived interferon-gamma (IFN-gamma) to the leukocyte-endothelial cell adhesion induced by hypercholesterolemia...

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..These findings suggest that superoxide derived from endothelial cell NADPH-oxidase and catalytically active iron contribute to the proinflammatory and prothrombogenic responses associated with sickle cell disease...

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..These results are consistent with leukocytes playing a major role in supporting I/R-induced platelet adhesion...

..This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion...

..berghei malaria was similar to that observed in control mice. Collectively, these results indicate that P-selectin is important for the development of malarial pathogenesis but is not required for leukocyte adhesion in brain...

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..T-cells seem to modulate the recruitment of neutrophils that occurs hours after reperfusion as well as the increased albumin extravasation that occurs within minutes after reperfusion...

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..Platelet- and T-lymphocyte-associated CD40L appears to play a major role in regulating the density of CD40 expression on vascular endothelial cells in vivo...

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..The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion...

..These findings implicate IL-12 in the inflammatory responses observed in the venules of hypercholesterolemic mice...

..The limited data available for the brain microcirculation support the potential of anti-leukocyte and anti-platelet strategies for stroke therapy...

..This anti-inflammatory effect likely involves the inhibition of P-selectin-mediated leukocyte and platelet adhesive interactions...

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..berghei malaria. Leukocyte rolling and adhesion in the brain vasculature during P. berghei malaria use different ligands than observed during inflammation in other vascular beds...

..pravastatin treatment inhibits the prothrombogenic effects of hypercholesterolemia via an action on both endothelial cells and platelets; and 3). the protective effect of pravastatin is nitric oxide dependent...

..These findings implicate a major role for both platelet-associated and endothelial cell-associated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R...

..CONCLUSIONS: The findings demonstrate that the pro-thrombogenic phenotype assumed in the microvasculature during hypercholesterolemia is largely attributed to leukocyte-dependent platelet adhesion...

..e. hypertension, diabetes, hypercholesterolaemia, and obesity, influence the vascular permeability response to I/R. Areas of uncertainty and controversy in this field of investigation are also identified...

..These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis...

..These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly alphanubeta3) and subsequent activation of FAK pathway...

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..Caveolin-1 (Cav-1), the major structural protein of caveolae in endothelial cells, is involved in the regulation of angiogenesis, so we investigated its role in experimental colitis...

..Evidence implicating regulatory T-cells as cerebroprotective modulators of the inflammatory and tissue injury responses to brain I/R support a continued focus on leukocytes as a target for therapeutic intervention in ischemic stroke...

..Chymase, a chymotrypsin-like protease, is a non-ACE angiotensin II (Ang II) generating enzyme. We determined if maternal chymotrypsin-like protease/chymase activity was increased in women with preeclampsia (PE)...

..These findings implicate both T and B cells and lymphocyte-derived IFN-gamma as mediators of the proinflammatory and prothrombogenic phenotype assumed by intestinal microvessels after I/R...

..We hypothesized that increased endothelial monolayer permeability in preeclampsia reflects altered monolayer barrier properties produced by disorganization of endothelial cell junction proteins...

..These findings indicate that neutrophil-derived superoxide plays a major role in the modulation of endotoxin-induced P/E adhesion...

..These findings indicate that 1) eNOS-derived NO attenuates endotoxin-induced P/E adhesion and 2) sGC is responsible for the antiadhesive action of NO...

..these results implicate trophoblast-derived factors in the increased vascular permeability associated with preeclampsia...

..These findings indicate that both alpha-subunits of the beta2-integrins contribute to the brain injury and blood cell-vessel wall interactions that are associated with transient focal cerebral ischemia...

..These common pathways of inflammation offer attractive targets for the development of drugs to combat cardiovascular disease and the associated ischemic disorders...

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..Insights gained from the characterization of the endothelial cell phenotype assumed by the preeclamptic microvasculature may lead to novel therapeutic strategies for the management of this syndrome...

..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...

..These findings indicate that the mechanism of blood cell-dependent arteriolar constriction during hypercholesterolemia may be dependent on thromboxane, a decrease in NO, and the proximity of the arterioles to postcapillary venules...

..4. The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease...

..DSS colitis was also associated with an increased expression of PSGL-1 in the colonic vasculature. These findings indicate that the recruitment of leukocytes and platelets in inflamed colonic venules are co-dependent processes...

..DISCUSSION: These findings indicate that both CD4(+) and CD8(+) T-cells contribute to granulocyte adhesion and emigration elicited in postcapillary venules by hypercholesterolemia...

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..The objective of this study was to determine whether the protein C pathway contributes to the enhanced extraintestinal thrombosis that is associated with dextran sodium sulfate (DSS)-induced colitis in mice...

..CONCLUSIONS: These findings indicate that vascular endothelial cells in most regional circulations assume an inflammatory phenotype and that cytokines and immune cells mediate this response in a tissue-specific manner...

..These findings implicate IL-1β as a mediator of enhanced microvascular thromboses that occur in extra-intestinal tissues during colonic inflammation...

..This study addresses the hypothesis that selectins mediate the recruitment of BMSCs into the postischemic cerebral microvasculature...

..NADPH oxidase-derived reactive oxygen species, produced by cells other than T lymphocytes, also appear critical for the Ang II-enhanced, T cell-dependent thrombosis response...

..The objective of this study was to define the role of the protein C pathway in the BBB permeability and edema elicited by experimental CVST. The role of neutrophil recruitment was also evaluated...

..Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha challenge may promote specific T lymphocyte recruitment in the inflamed colonic mucosa...

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..Collectively, these data point to a participation of CD40/CD40L in the angiogenic processes associated with mammary carcinogenesis of BALB/NeuT mice...

..Our objectives were to determine whether: (1) T-lymphocytes are the source of this IFN-gamma, and (2) whether T-cell-derived IFN-gamma also mediates the accompanying arteriolar dysfunction and platelet adhesion...

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..These findings indicate that lymphocytes mediate the microvascular dysfunction, but protect against the hepatocellular injury associated with murine sepsis...

..These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions...

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..The results obtained from the proposed studies should lead to an improved understanding of the mechanisms by which hypercholesterolemia exacerbates ischemic tissue injury. ..

..The proposed work should result in a better understanding of the nature and contribution of platelet activation and adhesion to the pathogenesis of IBD. ..

..The proposed work should lead to an improved understanding of the microvascular alterations that precede the appearance of overt large artery pathology during hypercholesterolemia. ..

..Furthermore, the proposed studies should improve our understanding of the factors responsible for the interstitial edema associated with various intestinal disorders...

..The results obtained should extend our understanding of the mechanisms underlying the enhanced vascular fluid and protein leakage and interstitial edema that accompanies an acute inflammatory response...

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