T Stevens

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..Adenylyl cyclase-to-cAMP phosphodiesterase ratios regulate cAMP at elevated levels compared with PAECs, which likely contribute to enhanced microvascular barrier function...

..Current concepts of mechanisms regulating endothelial cell barrier function were presented in a symposium at the 2000 Experimental Biology Conference and are reviewed here...

..Rather, development of novel therapeutics based upon anatomically restricted expression of molecular signatures may be developed to better combat vascular disease...

..A recent National Institutes of Health workshop was held to discuss emerging concepts in lung vascular biology. The findings of this workshop are summarized in this article...

..Thus, the present review summarizes our current understanding of pulmonary endothelial cell heterogeneity and discusses the potential role(s) of endothelial cell heterogeneity in the pathogenesis of pulmonary hypertension...

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..These data collectively support a role for endogenously expressed Trp1 in regulating a Ca2+-selective current activated upon Ca2+ store depletion...

..These results therefore support the growing paradigm that membrane and cytosolic cAMP pools target discrete effectors to control different physiological processes...

..This report is a synopsis of pertinent topics that were discussed, and future goals and research opportunities identified by the participants of the workshop are presented...

..Results indicate that the spectrin-protein 4.1 interaction selectively controls ISOC, indicating that physical coupling between calcium release and calcium entry is reliant upon the spectrin membrane skeleton...

..These findings demonstrate for the first time that the intracellular location of cAMP synthesis critically determines its physiological outcome...

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..Thus, inhibition of the TRPC1/TRPC4 channel provides a putative anti-inflammatory strategy...

..Thus, microtubule motor function plays an essential role in activating cytosolic calcium transitions through the membrane I(SOC) channel leading to endothelial barrier disruption...

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..Thus, our findings indicate that NAP1 functions as an important regulator of the proliferative and vasculogenic endothelial cell phenotype without globally impacting endothelial cell phenotype specification...

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..Thus the pulmonary microcirculation is enriched with EPCs that display vasculogenic competence while maintaining functional endothelial microvascular specificity...

..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...

..Thus, spectrin-anchored PDE4D4 shapes the physiological response to cAMP by directing it to barrier-enhancing effectors while limiting PKA-mediated microtubule reorganization...

..The concept of the endothelial cell as a "quasi-malignant" cell provides a new framework for antiproliferative, antiangiogenic therapy in severe PAH...

..These studies suggest that FXR may play a role in endothelial homeostasis and may serve as a novel molecular target for manipulating ET-1 expression in vascular EC...

..1 binding domain on TRPC4 or peptide competition to the protein 4.1 binding domain prevents ISOC activation. These findings reveal that interaction of protein 4.1 with TRPC4 is required for activation of the endothelial ISOC channel...

..Collectively, these data suggest that PDE5-regulated [cGMP]i controls endothelial cell growth and apoptosis, representing a mechanism of heterogeneity between two endothelial phenotypes...

..These studies provide a framework to understand how Prx1 controls EC differentiation and their subsequent incorporation into functional pulmonary vascular networks...

..Thus, PAECs and PMVECs differ in their structure and function, even under similar environmental conditions...

..We conclude that activation of the Cav3.1 channels selectively induces phenotypic changes in microvascular endothelial cells that mediate vaso-occlusion by sickled erythrocytes in the inflamed lung microcirculation...

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..1 mediates the physical communication between Ca2+ store depletion and channel activation. Thus, at present findings indicate a TRPC4-protein 4.1 physical linkage regulates I(SOC) activation following Ca2+ store depletion...

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..Thus, neutrophil adhesion through ICAM-1 induced signaling events leading to cytoskeletal changes only in PMECs, the site of neutrophil emigration and edema formation, and not in PAECs...

..These findings collectively illustrate a previously unrecognized mechanism of hyperpermeability induced by rises in cytosolic cAMP...

..This study is the first to localize ALCAM to endothelial cell junctions and demonstrate a functional relevance for co-expression of ALCAM by activated monocytes and endothelial cells...

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..The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value...

..Findings provide the first direct evidence that calcium inhibition of AC6 is essential for endothelial gap formation...

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..Proc Natl Acad Sci U S A 98: 9539-9544, 2001) and suggest that csPDI-mediated denitrosation helps to regulate the ability of the major plasma NO carrier (SNO-albumin) to transnitrosate endothelial cell molecular targets (e.g. MT)...

..Thus, this review summarizes data-emphasizing recent evidence in mammalian systems-implicating myosin motor function in the control of SOC entry...

..The proposed signaling pathway utilizes Stat3 as a fundamental signaling molecule that directs the production of the various centrosome proteins indirectly...

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..If true, then pharmacological inhibitors of this channel could be developed as a novel anti-inflammatory therapy. ..

..At the conclusion of this meeting and as part of the published report, we will have identified areas of need for future investigation in lung vascular biology. ..

..Completion of these studies may provide evidence of a Ca2+ channel that mediates Ca2+ entry in endothelial cells and is linked to control of cell shape and permeability. ..

..It is hoped completion of these studies will improve our understanding of mechanisms which regulate endothelial barrier properties so that effective therapies can be developed for treatment of non-cardiogenic pulmonary edema. ..

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