WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
Finnish physician who first described vascular hemophilia (1870-1949) (同)von_Willebrand, E. A. von Willebrand, Erik von Willebrand, Erik Adolf von Willebrand

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(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
verb / verso / 《話》very / velocity / volt[s] / volume / vide
…から(from),…の(of)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/20 10:27:19」(JST)

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Von Willebrand factor (vWF) (/ˌfʌnˈvɪlɨbrɑːnt/) is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome.^[1] Increased plasma levels in a large number of cardiovascular, neoplastic, and connective tissue diseases are presumed to arise from adverse changes to the endothelium, and may contribute to an increased risk of thrombosis.^{[citation needed]}

Biochemistry

Synthesis

vWF is a large multimeric glycoprotein present in blood plasma and produced constitutively as ultra-large vWF in endothelium (in the Weibel-Palade bodies), megakaryocytes (α-granules of platelets), and subendothelial connective tissue.^[1]

Structure

The basic vWF monomer is a 2050-amino acid protein. Every monomer contains a number of specific domains with a specific function; elements of note are:^[1]

the D'/D3 domain, which binds to factor VIII, (Von Willebrand factor type D domain)
the A1 domain, which binds to:
- platelet GPIb-receptor
- heparin
- possibly collagen
the A3 domain, which binds to collagen (Von Willebrand factor type A domain)
the C1 domain, in which the RGD domain binds to platelet integrin α_IIbβ₃ when this is activated
the "cysteine knot" domain (at the C-terminal end of the protein), which vWF shares with platelet-derived growth factor (PDGF), transforming growth factor-β (TGFβ) and β-human chorionic gonadotropin (βHCG, of pregnancy test fame). (Von Willebrand factor type C domain)

Monomers are subsequently N-glycosylated, arranged into dimers in the endoplasmic reticulum and into multimers in the Golgi apparatus by crosslinking of cysteine residues via disulfide bonds. With respect to the glycosylation, vWF is one of only a few proteins that carry ABO blood group system antigens.^[1]

Multimers of vWF can be extremely large, >20,000 kDa, and consist of over 80 subunits of 250 kDa each. Only the large multimers are functional. Some cleavage products that result from vWF production are also secreted but probably serve no function.^[1]

VWF monomer and multimers

Function

Von Willebrand factor's primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites.^[1] It is not an enzyme and, thus, has no catalytic activity.

vWF binds to a number of cells and molecules. The most important ones are:^[1]

Factor VIII is bound to vWF while inactive in circulation; factor VIII degrades rapidly when not bound to vWF. Factor VIII is released from vWF by the action of thrombin.
vWF binds to collagen, e.g., when it is exposed in endothelial cells due to damage occurring to the blood vessel.
vWF binds to platelet gpIb when it forms a complex with gpIX and gpV; this binding occurs under all circumstances, but is most efficient under high shear stress (i.e., rapid blood flow in narrow blood vessels, see below).
vWF binds to other platelet receptors when they are activated, e.g., by thrombin (i.e., when coagulation has been stimulated).

vWF plays a major role in blood coagulation. Therefore, vWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear in narrow vessels. From studies it appears that vWF uncoils under these circumstances, decelerating passing platelets.^[1] Calcium enhances the refolding rate of vWF A2 domain, allowing the protein to act as a shear force sensor. ^[2]

Catabolism

The biological breakdown (catabolism) of vWF is largely mediated by the enzyme ADAMTS13 (acronym of "a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13"). It is a metalloproteinase that cleaves vWF between tyrosine at position 842 and methionine at position 843 (or 1605–1606 of the gene) in the A2 domain. This breaks down the multimers into smaller units, which are degraded by other peptidases.^[3]

Role in disease

Hereditary or acquired defects of vWF lead to von Willebrand disease (vWD), a bleeding diathesis of the skin and mucous membranes, causing nosebleeds, menorrhagia, and gastrointestinal bleeding. The point at which the mutation occurs determines the severity of the bleeding diathesis. There are three types (I, II and III), and type II is further divided in several subtypes. Treatment depends on the nature of the abnormality and the severity of the symptoms.^[4] Most cases of vWD are hereditary, but abnormalities of vWF may be acquired; aortic valve stenosis, for instance, has been linked to vWD type IIA, causing gastrointestinal bleeding - an association known as Heyde's syndrome.^[5]

In thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), ADAMTS13 either is deficient or has been inhibited by antibodies directed at the enzyme. This leads to decreased breakdown of the ultra-large multimers of vWF and microangiopathic hemolytic anemia with deposition of fibrin and platelets in small vessels, and capillary necrosis. In TTP, the organ most obviously affected is the brain; in HUS, the kidney.^[6]

Higher levels of vWF are more common among people that have had ischemic stroke (from blood-clotting) for the first time. Occurrence is not affected by ADAMTS13, and the only significant genetic factor is the person's blood group.^[7]

History

vWF is named after Dr. Erik von Willebrand (1870–1949), a Finnish doctor who in 1924 first described a hereditary bleeding disorder in families from the Åland islands, who had a tendency for cutaneous and mucosal bleeding, including menorrhagia. Although von Willebrand could not identify the definite cause, he distinguished von Willebrand disease (vWD) from hemophilia and other forms of bleeding diathesis.^[8]

In the 1950s, vWD was shown to be caused by a plasma factor deficiency (instead of being caused by platelet disorders), and, in the 1970s, the vWF protein was purified.^[1]

Interactions

Von Willebrand factor has been shown to interact with Collagen, type I, alpha 1.^[9]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Sadler JE (1998). "Biochemistry and genetics of von Willebrand factor". Annu. Rev. Biochem. 67: 395–424. doi:10.1146/annurev.biochem.67.1.395. PMID 9759493.
^ Jakobi AJ, Mashaghi A, Tans SJ, Huizinga EG. Calcium modulates force sensing by the von Willebrand factor A2 domain. Nature Commun. 2011 Jul 12;2:385. [1]
^ Levy GG, Motto DG, Ginsburg D (2005). "ADAMTS13 turns 3". Blood 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620.
^ Sadler JE, Budde U, Eikenboom JC, et al. (2006). "Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor". J. Thromb. Haemost. 4 (10): 2103–14. doi:10.1111/j.1538-7836.2006.02146.x. PMID 16889557.
^ Vincentelli A, Susen S, Le Tourneau T, et al. (2003). "Acquired von Willebrand syndrome in aortic stenosis". N. Engl. J. Med. 349 (4): 343–9. doi:10.1056/NEJMoa022831. PMID 12878741.
^ Moake JL (2004). "von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura". Semin. Hematol. 41 (1): 4–14. doi:10.1053/j.seminhematol.2003.10.003. PMID 14727254.
^ Bongers T, de Maat M, van Goor M, et al. (2006). "High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability". Stroke 37 (11): 2672–7. doi:10.1161/01.STR.0000244767.39962.f7. PMID 16990571.
^ von Willebrand EA (1926). "Hereditär pseudohemofili". Fin Läkaresällsk Handl 68: 87–112. Reproduced in Von Willebrand EA (1999). "Hereditary pseudohaemophilia". Haemophilia 5 (3): 223–31; discussion 222. doi:10.1046/j.1365-2516.1999.00302.x. PMID 10444294.
^ Pareti FI, Fujimura Y, Dent JA, Holland LZ, Zimmerman TS, Ruggeri ZM (1986). "Isolation and characterization of a collagen binding domain in human von Willebrand factor". J. Biol. Chem. 261 (32): 15310–5. PMID 3490481.

External links

GeneReviews/NCBI/NIH/UW entry on von Willebrand Factor Deficiency. Includes: Type 1 von Willebrand Disease, Type 2A von Willebrand Disease, Type 2B von Willebrand Disease, Type 2M von Willebrand Disease, Type 2N von Willebrand Disease, Type 3 von Willebrand Disease

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. von Willebrand因子の生物学および正常機能 biology and normal function of von willebrand factor
2. von Willebrand病の臨床症状および診断 clinical presentation and diagnosis of von willebrand disease
3. von Willebrand病の治療 treatment of von willebrand disease
4. HIV感染患者における心血管疾患の病因およびバイオマーカー pathogenesis and biomarkers of cardiovascular disease in hiv infected patients
5. von Willebrand病の分類および病態生理 classification and pathophysiology of von willebrand disease

English Journal

Heparanase procoagulant activity, factor Xa, and plasminogen activator inhibitor 1 are increased in shift work female nurses.

Nadir Y1, Saharov G, Hoffman R, Keren-Politansky A, Tzoran I, Brenner B, Shochat T.
Annals of hematology.Ann Hematol.2015 Jul;94(7):1213-9. doi: 10.1007/s00277-015-2345-8. Epub 2015 Mar 7.
Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underling mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation syst
PMID 25743687

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network.

Holm E1, Abshire TC, Bowen J, Álvarez MT, Bolton-Maggs P, Carcao M, Federici AB, Gill JC, Halimeh S, Kempton C, Key NS, Kouides P, Lail A, Landorph A, Leebeek F, Makris M, Mannucci P, Mauser-Bunschoten EP, Nugent D, Valentino LA, Winikoff R, Berntorp E.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2015 Jun;26(4):383-8. doi: 10.1097/MBC.0000000000000257.
Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed
PMID 25688461

Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma: a case report.

Vinholt PJ1, Nybo M.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2015 Jun;26(4):454-7. doi: 10.1097/MBC.0000000000000240.
We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays, and se
PMID 25485787

Japanese Journal

若年性皮膚筋炎に合併した急速進行性間質性肺炎の1男児例

石川順一,鹿間芳明,高橋英彦 [他]
日本小児科学会雑誌 115(4), 793-799, 2011-04
NAID 40018827527

重症急性膵炎におけるADAMTS13活性の動態とその臨床的意義 (特集重症急性膵炎の病態解明と治療の新展開)

森岡千惠,植村正人,高谷広章 [他]
消化器内科 52(2), 200-208, 2011-02
NAID 40018768280

Related Pictures

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リンク元	「血液凝固因子」「フォンウィルブランド因子」「第VIII因子」「VWF」
拡張検索	「ristocetin co factor activity in von Willebrand factor」
関連記事	「fact」「factor」「Willebrand」「VON」

「血液凝固因子」

Von Willebrand factor
	; PDB rendering based on 1ao3.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1AO3, 1ATZ, 1AUQ, 1FE8, 1FNS, 1IJB, 1IJK, 1M10, 1OAK, 1SQ0, 1U0N, 1UEX, 2ADF, 2MHP, 2MHQ, 3GXB, 3HXO, 3HXQ, 3PPV, 3PPW, 3PPX, 3PPY, 3ZQK, 4C29, 4C2A, 4C2B, 4DMU, 4NT5
Identifiers
Symbols	VWF ; F8VWF; VWD
External IDs	OMIM: 613160 MGI: 98941 HomoloGene: 466 GeneCards: VWF Gene
Gene ontology
Molecular function	• glycoprotein binding; • protease binding; • integrin binding; • protein binding; • collagen binding; • immunoglobulin binding; • identical protein binding; • protein homodimerization activity; • protein N-terminus binding; • chaperone binding;
Cellular component	• extracellular region; • proteinaceous extracellular matrix; • endoplasmic reticulum; • external side of plasma membrane; • extracellular matrix; • platelet alpha granule; • platelet alpha granule lumen; • Weibel-Palade body; • extracellular vesicular exosome;
Biological process	• liver development; • placenta development; • platelet degranulation; • cell adhesion; • blood coagulation; • blood coagulation, intrinsic pathway; • hemostasis; • response to wounding; • platelet activation; • extracellular matrix organization; • cell-substrate adhesion; • protein homooligomerization;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

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英: coagulation factor (Z), clotting factor, blood coagulation factor, blood coagulation factors
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