Systemic antithrombotic effects of ADAMTS13

被引：190

作者：

Chauhan, AK

Motto, DG

Lamb, CB

Bergmeier, W

Dockal, M

Plaimauer, B

Scheiflinger, F

Ginsburg, D

Wagner, DD ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[3] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[5] Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[6] BAxter Biosci, A-1220 Vienna, Austria

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2006年 / 203卷 / 03期

关键词：

D O I：

10.1084/jem.20051732

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats 13) cleaves highly adhesive large von Willebrand factor (VWF) multimers after their release from the endothelium. ADAMTS13 deficiency is linked to a life-threatening disorder, thrombotic thrombocytopenic purpura (TTP), characterized by platelet-rich thrombi in the microvasculature. Here, we show spontaneous thrombus formation in activated microvenules of Adamts13(-/-) mice by intravital microscopy. Strikingly, we found that ADAMTS13 down-regulates both platelet adhesion to exposed subendothelium and thrombus formation in injured arterioles. An inhibitory antibody to ADAMTS13 infused in wild-type mice prolonged adhesion of platelets to endothelium and induced thrombi formation with embolization in the activated microvenules. Absence of ADAMTS13 did not promote thrombi formation in alpha IIb beta 3 integrin-inhibited blood. Recombinant ADAMTS13 reduced platelet adhesion and aggregation in histamine-activated venules and promoted thrombus dissolution in injured arterioles. Our findings reveal that ADAMTS13 has a powerful natural antithrombotic activity and recombinant ADAMTS13 could be used as an antithrombotic agent.

引用

页码：767 / 776

页数：10

共 50 条

[1] The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction
Austin, S. K.
Starke, R. D.
Lawrie, A. S.
Cohen, H.
Machin, S. J.
Mackie, I. J.
BRITISH JOURNAL OF HAEMATOLOGY, 2008, 141 (04) : 536 - 544
[2] ADAMTS13 in nephrology [ADAMTS13 in der Nephrologie]
Bockmeyer C.L.
Modde F.
Becker J.U.
Der Nephrologe, 2013, 8 (1): : 69 - 70
[3] ADAMTS13 and TTP
Zheng, XL
Majerus, EM
Sadler, JE
CURRENT OPINION IN HEMATOLOGY, 2002, 9 (05) : 389 - 394
[4] ADAMTS13 Alone
George, James N.
BLOOD, 2010, 116 (12) : 2003 - 2004
[5] ADAMTS13 INHIBITOR ASSESSMENT WITH THE HEMOSIL ACUSTAR ADAMTS13 ACTIVITY ASSAY
Valsecchi, C.
Mirabet, M.
Mancini, I.
Schiavone, L.
Mane-Padros, D.
Peyvandi, F.
HAEMATOLOGICA, 2019, 104 : 23 - 24
[6] Spectrum of ADAMTS13 gene mutations in 19 patients with ADAMTS13 deficiency
Calderzzo, J. C.
Kempfer, A. C.
Keller, L.
Luceros, Sanchez A.
Woods, A., I
Powazniak, Y. P.
Lazzari, M. A.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 : 656 - 656
[7] SNPs in ADAMTS13
Tseng, Sandra Chang
Kimchi-Sarfaty, Chava
PHARMACOGENOMICS, 2011, 12 (08) : 1147 - 1160
[8] Variants in ADAMTS13 and Smoking Contribute to Plasma ADAMTS13 Level Variation
Desch, Karl C.
Ma, Qianyi
Ozel, Ayse Bilge
McGee, Beth M.
Siemieniak, David R.
Li, Jun Z.
Ginsburg, David
BLOOD, 2014, 124 (21)
[9] ADAMTS13 deficiency and immunological abnormalities in patients with systemic sclerosis
Gerlicz-Kowalczuk, Zofia
Torzecka, Jolanta D.
Dziankowska-Zaborszczyk, Elzbieta
Ograczyk, Alicja
Zalewska-Janowska, Anna M.
Woznicka, Anna
Dziankowska-Bartkowiak, Bozena
POSTEPY DERMATOLOGII I ALERGOLOGII, 2018, 35 (02): : 182 - 184
[10] Low ADAMTS13 antigen and activity and the presence of ADAMTS13 autoantibody suggest ADAMTS13 may play a role in venous thromboembolism
Fryer, H. J. L.
Hoecke, C. J.
Wu, J. R.
Guinto, E.
Greenfield, R. S.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 : 426 - 426

← 1 2 3 4 5 →