Changes in the pattern of distribution of von Willebrand factor in rat aortic endothelial cells following thrombin generation <i>in vivo</i>

Senis, Yotis A.; Richardson, Mary; Tinlin, Shawn; Maurice, Donald H.; Giles, Alan R.

doi:10.1046/j.1365-2141.1996.4661005.x

Cited by 29 publications

(24 citation statements)

References 32 publications

(49 reference statements)

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“…111 In en face Hautchen preparations of rat aorta, only 20% to 50% of ECs were shown to be positive for vWF as detected by immunohistochemistry. 112 vWF positivity occurred in groups of cells orientated along the longitudinal axis of the aorta but was scant at sites of intercostal orifices. 112 Systemic administration of lipopolysaccharide in mice resulted in upregulation of vWF mRNA in heart and kidney but decreased expression in the lung, aorta, brain, and adipose tissue.…”

Section: Hemostasismentioning

confidence: 99%

“…112 vWF positivity occurred in groups of cells orientated along the longitudinal axis of the aorta but was scant at sites of intercostal orifices. 112 Systemic administration of lipopolysaccharide in mice resulted in upregulation of vWF mRNA in heart and kidney but decreased expression in the lung, aorta, brain, and adipose tissue. 111 In mice, t-PA expression in the endothelium was reported to be restricted to arteries of the pulmonary system and central nervous system.…”

Section: Hemostasismentioning

confidence: 99%

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Phenotypic Heterogeneity of the Endothelium

Aird

2007

Circulation Research

1,484

862

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Abstract-Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the first of a 2-part review focused on phenotypic heterogeneity of blood vessel endothelium. This review provides an historical perspective of our understanding of endothelial heterogeneity, discusses the scope of phenotypic diversity across the vascular tree, and addresses proximate and evolutionary mechanisms of endothelial cell heterogeneity. The overall goal is to underscore the importance of phenotypic heterogeneity as a core property of the endothelium. (Circ Res. 2007;100:158-173.)

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Section: Hemostasismentioning

confidence: 99%

Section: Hemostasismentioning

confidence: 99%

Phenotypic Heterogeneity of the Endothelium

Aird

2007

Circulation Research

1,484

862

View full text Add to dashboard Cite

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“…5,6 Third, vWf expression is particularly prominent near branch points and bifurcations, areas prone to atherosclerotic lesion development. 7 Fourth, platelets may contribute to the atherosclerotic process by releasing growth factors after their vWf-dependent interaction with a damaged endothelial surface. 8,9 Experimental studies performed in pigs with von Willebrand disease (vWd), though supportive of a role for vWf in atherosclerosis, 3 have not been conclusive because of the genetic heterogeneity existing among the animals.…”

Section: Introductionmentioning

confidence: 99%

Localized reduction of atherosclerosis in von Willebrand factor–deficient mice

Methia

André

Denis

et al. 2001

Blood

189

153

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To examine the role of the platelet adhesion molecule von Willebrand factor (vWf) in atherogenesis, vWf-deficient mice (vWf؊/؊) were bred with mice lacking the low-density lipoprotein receptor (LDLR؊/؊) on a C57BL/6J background. LDLR؊/؊vWf؉/؉ and LDLR؊/؊vWf؊/؊ mice were placed on a diet rich in saturated fat and cholesterol for different lengths of time. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules in both genotypes, indicating an increase in P-selectin-mediated adhesion to the endothelium. After 8 weeks on the atherogenic diet, the fatty streaks formed in the aortic sinus of LDLR؊/؊vWf؊/؊ mice of either sex were 40% smaller and contained fewer monocytes than those in LDLR؊/؊vWf؉/؉ mice. After 22 weeks on the atherogenic diet (early fibrous plaque stage), the difference in lesion size in the aortic sinus persisted. Interestingly, the lesion distribution in the aortas of LDLR؊/؊vWf؊/؊ animals was different from that of LDLR؊/؊ vWf؉/؉ animals. In vWf-positive mice, half of all lesions were located at the branch points of the renal and mesenteric arteries, whereas lesions in this area were not as prominent in the vWf-negative mice. These results indicate that the absence of vWf primarily affects the regions of the aorta with disturbed flow that are prone to atherosclerosis. Thus, vWf may recruit platelets/leukocytes to the lesion in a flow-dependent manner or may be part of the mechano-transduction pathway regulating endothelial response to shear stress. Introductionvon Willebrand factor (vWf) is a multimeric glycoprotein essential for thrombus formation at high shear stress. 1 It is found in plasma, platelet ␣-granules, Weibel-Palade bodies of endothelial cells, and the subendothelium. 2 Even though the involvement of vWf in thrombus formation at the site of atherosclerotic plaque rupture is well established, 3 the role of vWf in atherosclerotic lesion development is less clear. Several indications suggest that vWf may directly participate in plaque formation. First, Weibel-Palade bodies are found in great number at the sites of atherosclerotic lesions. 4 Second, oxidized low-density lipoprotein (LDL) and fluid mechanics, 2 factors involved in atherosclerotic lesion development, can induce Weibel-Palade body exocytosis. 5,6 Third, vWf expression is particularly prominent near branch points and bifurcations, areas prone to atherosclerotic lesion development. 7 Fourth, platelets may contribute to the atherosclerotic process by releasing growth factors after their vWf-dependent interaction with a damaged endothelial surface. 8,9 Experimental studies performed in pigs with von Willebrand disease (vWd), though supportive of a role for vWf in atherosclerosis, 3 have not been conclusive because of the genetic heterogeneity existing among the animals. 10 The recent generation of vWf-deficient mice has provided an opportunity to directly test the importance of vWf in atherosclerosis. Because mice are resistant to atherosclerosis, the vWf-deficient mice were first bred with an atherosclerosis...

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“…Expression of vWF also varies between neighboring endothelial cells. 5 The elucidation of the mechanisms underlying vWF expression may provide important insights into the molecular basis of vascular diversity.The structural organization of the mouse, human, and bovine vWF promoter-proximal region is closely related. [6][7][8] The first exon (11 to 1 246 in human vWF) encodes the 59 untranslated sequence.…”

mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium

Yuan

Janes

Beeler

et al. 2013

Blood

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Key Points• RNA splicing of the first intron of the von Willebrand factor gene is essential for expression in the endothelium.• RNA splicing may play a role in mediating endothelial cell heterogeneity.We previously demonstrated that the first intron of the human von Willebrand factor (vWF) is required for gene expression in the endothelium of transgenic mice. Based on this finding, we hypothesized that RNA splicing plays a role in mediating vWF expression in the vasculature. To address this question, we used transient transfection assays in human endothelial cells and megakaryocytes with intron-containing and intronless human vWF promoter-luciferase constructs. Next, we generated knockin mice in which LacZ was targeted to the endogenous mouse vWF locus in the absence or presence of the native first intron or heterologous introns from the human b-globin, mouse Down syndrome critical region 1, or hagfish coagulation factor X genes. In both the in vitro assays and the knockin mice, the loss of the first intron of vWF resulted in a significant reduction of reporter gene expression in endothelial cells but not megakaryocytes. This effect was rescued to varying degrees by the introduction of a heterologous intron. Intron-mediated enhancement of expression was mediated at a posttranscriptional level. Together, these findings implicate a role for intronic splicing in mediating lineage-specific expression of vWF in the endothelium. (Blood. 2013;121(21):4404-4412) Introduction Von Willebrand factor (vWF) is a plasma protein that mediates platelet hemostatic function and stabilizes coagulation factor VIII. vWF plays a particularly important role in platelet adhesion and aggregation at sites of high shear rates.1 Expression of vWF is restricted to endothelial cells and platelets. vWF is differentially expressed in the vasculature. For example, vWF protein and mRNA levels are higher in veins, compared with arteries, 2,3 and in venules compared with arterioles. 4 Within the microvasculature, vWF is expressed at particularly low levels in the liver. Expression of vWF also varies between neighboring endothelial cells. 5 The elucidation of the mechanisms underlying vWF expression may provide important insights into the molecular basis of vascular diversity.The structural organization of the mouse, human, and bovine vWF promoter-proximal region is closely related. [6][7][8] The first exon (11 to 1 246 in human vWF) encodes the 59 untranslated sequence. The second exon contains the ATG translational start site. Exons 1 and 2 are separated by an intron (1247 to 11475 in human vWF). To study mechanisms of vWF gene regulation, we have previously used a plug-insocket approach in which a single copy of a vWF promoter-LacZ cassette is targeted to the Hprt locus of mice. Using this strategy, we showed that a region of the human vWF gene (termed vWF2, between 22182 and the end of the first intron) directed expression in the vasculature of the brain, heart and skeletal muscle, but not in other organs such as aorta, lung, liver, spleen, ...

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Changes in the pattern of distribution of von Willebrand factor in rat aortic endothelial cells following thrombin generation in vivo

Cited by 29 publications

References 32 publications

Phenotypic Heterogeneity of the Endothelium

Phenotypic Heterogeneity of the Endothelium

Localized reduction of atherosclerosis in von Willebrand factor–deficient mice

Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium

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