Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo.
von Willebrand factor (vWF) is frequently used as a biochemical marker for endothelial cells (ECs). Despite this, little is known about the relative level of expression and regulation of this hemostatic factor in ECs in different vascular beds in vivo. In the present study, we used quantitative reverse transcription polymerase chain reaction and in situ hybridization analysis to study vWF gene expression in murine tissues. Large differences in the level of vWF mRNA were observed when comparing highly vascularized tissues, with the lung and brain containing 5 to 50 times higher concentrations of vWF mRNA than the kidney and liver. In this regard, ECs of small vessels and some microvessels in the lung and brain expressed abundant vWF mRNA, whereas ECs of similar sized vessels in the liver and kidney expressed relatively low levels. In general, significantly higher levels of vWF mRNA and antigen were demonstrated in ECs of larger vessels compared with microvessels and in venous ECs compared with arterial ECs. Although intraperitoneal administration of endotoxin (or tumor necrosis factor-alpha) increased plasma vWF levels, it had variable effects on the steady-state level of vWF mRNA in murine tissues (ie, it decreased vWF mRNA in many tissues, increased it in others, and had little effect on still others). These results indicate that vWF is differentially expressed and regulated in ECs present in different tissues and within the same vascular bed.
Department of Vascular Biology (VB-3), The Scripps Research Institute, La Jolla, CA, USA.
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K
Yamamoto
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V
de Waard
C
C
Fearns
D J
DJ
Loskutoff
D000818:Animals; D001921:Brain / Q000098:blood supply; D004730:Endothelium, Vascular / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism; D005786:Gene Expression Regulation; D006487:Hemostasis; D017403:In Situ Hybridization; D007668:Kidney / Q000098:blood supply; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000098:blood supply; D008168:Lung / Q000098:blood supply; D008221:Lymphoid Tissue / Q000098:blood supply; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor