Genetic background determines response to hemostasis and thrombosis

Hoover‐Plow, Jane; Shchurin, Aleksey; Hart, Erika; Sha, Jingfeng; Hill, Annie E.; Singer, Jonathan B.; Nadeau, Joseph H.

doi:10.1186/1471-2326-6-6

Cited by 34 publications

(60 citation statements)

References 51 publications

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“…38 Our observation that bleeding time is reduced in S100A10 Ϫ/Ϫ mice, compared with WT mice, is consistent with the decreased fibrinolysis exhibited by the S100A10 Ϫ/Ϫ mice. Bleeding time has been shown to be significantly increased in the Pg Ϫ/Ϫ mice compared with WT mice, 39 whereas another group found no To detect the total cellular levels of annexin A2 and S100A10, primary murine endothelial cells, isolated from WT or S100A10 Ϫ/Ϫ mice (A), as well as control and S100A10 depleted TIME cells (B), were dissociated from culture flasks, lysed, subjected to SDS-PAGE, and immunoblotted with antiactin (loading control), antiannexin A2, or anti-S100A10 antibodies. Cell-surface protein levels for primary murine endothelial cells (C) and TIME cells (D), as detected by cell-surface biotinylation, are shown.…”

Section: S100a10 and Fibrinolysis 3177mentioning

confidence: 99%

“…40 The interpretation of the Pg Ϫ/Ϫ mice data was complicated by the possible role of Pg in platelet function. 39 However, S100A10 has not been detected in platelets, suggesting that loss of S100A10 is unlikely to affect platelet function. 41 In support of the decreased bleed time being caused by decreased fibrinolysis is the report that textilinin-1, a potent Pm inhibitor from Pseudonaja textilis venom, dramatically decreases the bleeding time.…”

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confidence: 99%

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Regulation of fibrinolysis by S100A10 in vivo

Surette

Madureira

Phipps

et al. 2011

Blood

111

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Endothelial cells form the inner lining of vascular networks and maintain blood fluidity by inhibiting blood coagulation and promoting blood clot dissolution (fibrinolysis). Plasmin, the primary fibrinolytic enzyme, is generated by the cleavage of the plasma protein, plasminogen, by its activator, tissue plasminogen activator. This reaction is regulated by plasminogen receptors at the surface of the vascular endothelial cells. Previous studies have identified the plasminogen receptor protein S100A10 as a key regulator of plasmin generation by cancer cells and macrophages. Here we examine the role of S100A10 and its annexin A2 binding partner in endothelial cell function using a homozygous S100A10-null mouse. Compared with wild-type mice, S100A10-null mice displayed increased deposition of fibrin in the vasculature and reduced clearance of batroxobin-induced vascular thrombi, suggesting a role for S100A10 in fibrinolysis in vivo. Compared with wild-type cells, endothelial cells from S100A10-null mice demonstrated a 40% reduction in plasminogen binding and plasmin generation in vitro. Furthermore, S100A10-deficient endothelial cells demonstrated impaired neovascularization of Matrigel plugs in vivo, suggesting a role for S100A10 in angiogenesis. These results establish an important role for S100A10 in the regulation of fibrinolysis and angiogenesis in vivo, suggesting S100A10 plays a critical role in endothelial cell function. (Blood. 2011;118(11): 3172-3181)

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Section: S100a10 and Fibrinolysis 3177mentioning

confidence: 99%

mentioning

confidence: 99%

Regulation of fibrinolysis by S100A10 in vivo

Surette

Madureira

Phipps

et al. 2011

Blood

111

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“…63 The development and use of multiple recombinant inbred lines and chromosomal substitution strains are already underway to map strain modifiers of hemostasis. 64,65 …”

Section: Spontaneous Thrombosismentioning

confidence: 99%

Murine Models of Vascular Thrombosis

Westrick

Winn

Eitzman

2007

ATVB

168

160

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Abstract-Thrombotic complications of vascular disease are the leading cause of morbidity and mortality in most industrialized countries. Despite this, safe and effective drugs targeting these complications are limited, especially in the chronic setting. This is because of the complexity of thrombosis in both arteries and veins, which is becoming increasingly evident as numerous factors are now known to affect the fate of a forming thrombus. To fully characterize thrombus formation in these settings, in vivo models are necessary to study the various components and intricate interactions that are involved. Genetic manipulations in mice are greatly facilitating the dissection of relevant pro-and antithrombotic influences. Standardized models for the study of thrombosis in mice as well as evolving techniques that allow imaging of molecular events during thrombus formation are now available. This review will highlight some of the recent developments in the field of thrombosis using mouse models and how these studies are expanding our knowledge of thrombotic disease. (Arterioscler Thromb Vasc

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“…Polymorphisms exist for substrains of the same inbred strains [8]. Genetic background also influences pathways that regulate thrombosis and hemostasis: differences were observed in global bleeding and thrombosis assays [9], coagulation and fibrinolytic factors [10], and susceptibility to treatment [11].To investigate the ability of the tail-tip bleeding assay to detect the influence of genetic background on bleeding phenotype, we used hemophilic mice on different backgrounds, i.e. coagulation factor VIII (exon 17) knockout (FVIII À/À ) [12] mice on a BALB/c, C57BL/6, or mixed background, along with different substrains of wild-type C57BL/6 or BALB/c mice ( Table 1).…”

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confidence: 99%

Influence of genetic background on bleeding phenotype in the tail‐tip bleeding model and recommendations for standardization: communication from the SSC of the ISTH

Schiviz

Magirr

Leidenmühler

et al. 2014

Journal of Thrombosis and Haemostasis

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The murine tail-tip bleeding model is widely used to measure bleeding time, blood loss, and survival after treatment [1][2][3][4]. Because of the considerable variation in data from these studies and thus the need for large sample sizes per group, and the lack of comparability of results from different laboratories, research groups have tried to standardize the model. In 2010, the SSC of the ISTH proposed standardized methods for determining tail bleeding time in mice. The SSC report standardized the tail clipping by endorsing the use of a warming chamber to evenly warm the anesthetized mouse, and assessing the influence of anesthesia and systolic blood pressure on blood loss [5].We sought to test the ability of the standardized method to detect differences in bleeding phenotypes of wild-type mouse strains, which may show different bleeding phenotypes [6]. The relevance of the genetic background of inbred mouse strains or transgenic mice on phenotype has been described in various research fields. Mice may differ in physiologic parameters [7] or in response to triggers. Polymorphisms exist for substrains of the same inbred strains [8]. Genetic background also influences pathways that regulate thrombosis and hemostasis: differences were observed in global bleeding and thrombosis assays [9], coagulation and fibrinolytic factors [10], and susceptibility to treatment [11].To investigate the ability of the tail-tip bleeding assay to detect the influence of genetic background on bleeding phenotype, we used hemophilic mice on different backgrounds, i.e. coagulation factor VIII (exon 17) knockout (FVIII À/À ) [12] mice on a BALB/c, C57BL/6, or mixed background, along with different substrains of wild-type C57BL/6 or BALB/c mice ( Table 1). The mice were anesthetized with 100 mg kg -1 ketamine and 10 mg kg -1 xylazine and placed in a warming chamber. Two millimeters of the tail tip were clipped with a guillotine [4], the tails were immersed in warm saline (2 mL, 35 AE 2°C), and blood was collected over a period of 60 min; anesthesia was maintained as required by subcutaneous supplementation with one-third of the starting dose. Blood loss was determined gravimetrically. At the end of this observation period, the mice were removed from the chamber and humanely killed by cervical dislocation. Pairwise tests of equality of variance were performed with a bootstrap approach; the level of statistical significance was set to P = 0.05.C.FVIII À/À mice showed markedly lower median blood loss (365.7 mg) than B6.FVIII À/À (965.2 mg) and B6; FVIII À/À (890.4 mg) mice. For all three strains, median blood loss was lower in females than in males, with the largest sex difference (634 mg vs. 954 mg for females vs. males) and the highest interindividual variation being observed in B6;FVIII À/À mice (Fig. 1). In 129S1/SvmJ mice and the four substrains of BALB/c mice, median blood loss (23.5 mg and 10.0-19.0 mg, respectively) and interanimal variability were low. In contrast, median blood loss in C57BL/6 substrains varied from 36.0 mg (C57BL/...

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Genetic background determines response to hemostasis and thrombosis

Cited by 34 publications

References 51 publications

Regulation of fibrinolysis by S100A10 in vivo

Regulation of fibrinolysis by S100A10 in vivo

Murine Models of Vascular Thrombosis

Influence of genetic background on bleeding phenotype in the tail‐tip bleeding model and recommendations for standardization: communication from the SSC of the ISTH

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