Abstract:
RATIONALE:Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. OBJECTIVE:We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. METHODS AND RESULTS:In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava. We demonstrated that 2 strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. MCs were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the inferior vena cava wall after DVT induction were reduced in MC-deficient mice. Stenosis application increased plasma levels of soluble P-selectin in wild-type but not in MC-deficient mice. MC releasate elevated ICAM-1 (intercellular adhesion molecule-1) expression on HUVEC (human umbilical vein endothelial cells) in vitro. Topical application of compound 48/80, an MC secretagogue, or histamine, a Weibel-Palade body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine restored thrombosis in MC-deficient animals. CONCLUSIONS:MCs exacerbate DVT likely through endothelial activation and Weibel-Palade body release, which is, at least in part, mediated by histamine. Because MCs do not directly contribute to normal hemostasis, they can be considered potential targets for prevention of DVT in humans.
journal_name
Circ Resjournal_title
Circulation researchauthors
Ponomaryov T,Payne H,Fabritz L,Wagner DD,Brill Adoi
10.1161/CIRCRESAHA.117.311185subject
Has Abstractpub_date
2017-09-29 00:00:00pages
941-950issue
8eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.117.311185journal_volume
121pub_type
杂志文章abstract:RATIONALE:7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. OBJECTIVE:We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. ME...
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更新日期:1985-10-01 00:00:00
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更新日期:2019-03-01 00:00:00
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pub_type: 杂志文章,评审
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doi:10.1161/01.res.71.4.906
更新日期:1992-10-01 00:00:00
abstract::High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses...
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更新日期:1992-02-01 00:00:00
abstract::The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from ...
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更新日期:1989-10-01 00:00:00
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更新日期:1979-10-01 00:00:00
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更新日期:1976-09-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:1999-06-11 00:00:00
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更新日期:1994-04-01 00:00:00
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更新日期:1991-08-01 00:00:00