Deep vein thrombosis resolution is impaired in diet-induced type 2 diabetic mice

Bouzeghrane, Fatiha; Zhang, Xiaochun; Gevry, Guylaine

doi:10.1016/j.jvs.2008.07.050

Cited by 17 publications

(13 citation statements)

References 45 publications

(82 reference statements)

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“…[29][30][31] In dietinduced type 2 diabetic mice, both the intensity of macrophage infiltration and impaired fibrinolysis, as reflected by the measurement of the uPA/PAI-1 ratio, were found to be involved in impaired resolution of deep vein thrombosis. 32 In the present study, VLCD induces a 38% reduction in PAI-levels, a result in line with previously published data. 33 As adipocytes represent an important source of PAI-1 synthesis, changes in PAI-1 levels are commonly purported to mainly reflect weight loss rather than a diminished insulin resistance.…”

Section: Consequences Of Weight Reduction On Platelet Activationsupporting

confidence: 93%

Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles

et al. 2011

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Background: In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth. Objectives: In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage. Methods: Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays. Results: A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4 kg m À2 were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r ¼ 0.534; P ¼ 0.010) and at 90 days follow-up (r ¼ 0.487; P ¼ 0.021). At 90 days, weight reduction (À9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (À38%), procoagulant platelet-derived MPs (À43%), leukocyte-derived MPs (À28%) and leptin (À32%) levels. Conclusion: In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.

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Section: Consequences Of Weight Reduction On Platelet Activationsupporting

confidence: 93%

Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles

et al. 2011

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“…The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage such as acute coronary syndrome or diabetes mellitus [13][14][15][16][17] . These pathological situations are typically characterized by higher levels of both coagulation endothelial markers and MMPs.…”

Section: Discussionmentioning

confidence: 71%

The Pathophysiology of Endothelial Function in Pregnancy and the Usefulness of Endothelial Markers

Slavík¹,

Procházková²,

Procházka³

et al. 2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aim. The aim of this study was to assess coagulation markers of endothelial damage and examine new markers of endothelial activation such as matrix metalloproteinases (MMPs) in a group of healthy pregnant women. Matrix metalloproteinase (MMP)-2, in particular, plays a major role in the degradation of the extracellular matrix confirming its essential function in both the survival (angiogenesis) and death of endothelial cells.Detection of specific coagulation factors, mainly released from the vascular endothelium such as vWF, sTM (soluble thrombomodulin) and ePCR (endothelial protein C receptor) and factors dependent on endothelial activation such as t-PA and PAI-1, could provide information on possible endothelial dysfunction and help differentiate pregnant patients with an altered thrombotic state.Methods. Healthy pregnant women underwent complete assessment for endothelial damage (as vWF, vWF activity, sTM, ePCR, EMP, MMP-2, MMP-9 and TIMP-2) using the ELISA and other methods.Results and Conclusions. The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage and typically characterized by higher levels of both coagulation endothelial markers and MMPs. In pregnancy, changes in extracellular matrix composition and matrix metalloproteinase activity also occur and promote vascular remodeling but, only in the uterus. Predisposing risk factors for epithelial dysfunction, and vascular mediators associated with vascular remodeling must be assessed from concentrations in whole blood. The levels of MMPs are not increased in the circulation and the local situation in the uterus cannot be monitored this way.However, MMP-2 processes and modulates the functions of many other vasoactive and pro-inflammatory molecules including adrenomedullin, big endothelin-1, calcitonin gene-related peptide, CCL7/MCP-3, CXCL12/SDF-1, galectin-3, IGFBP-3, IL-1 Beta, S100A8, and S100A9. These molecules represent new potential molecular markers of endothelial damage during pregnancy.

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“…The justification for the use of the model is that it is considered a good model to observe increased number of microparticles and has been reported extensively elsewhere [21,22,24]. Accompanying the MPs observations we also present electron microscopy observations from mouse platelets and leukocytes, cells that participate in thrombus formation.…”

Section: Introductionmentioning

confidence: 85%

“…In this study, MPs were generated using a well-documented mouse inferior vena cava (IVC) ligation model of DVT [20,21,22,23,24]. The justification for the use of the model is that it is considered a good model to observe increased number of microparticles and has been reported extensively elsewhere [21,22,24].…”

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Mouse Deep Vein Thrombosis Derived Microparticles by Differential Filtration with Nanopore Filters

Peramo

Díaz

2011

Membranes

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With the objective of making advancements in the area of pro-thrombotic microparticle characterization in cardiovascular biology, we present a novel method to separate blood circulating microparticles using a membrane-based, nanopore filtration system. In this qualitative study, electron microscopy observations of these pro-thrombotic mouse microparticles, as well as mouse platelets and leukocytes obtained using a mouse inferior vena cava ligation model of deep-vein thrombosis are presented. In particular, we present mouse microparticle morphology and microstructure using SEM and TEM indicating that they appear to be mostly spherical with diameters in the 100 to 350 nm range. The nanopore filtration technique presented is focused on the development of novel methodologies to isolate and characterize blood circulating microparticles that can be used in conjunction with other methodologies. We believe that determination of microparticle size and structure is a critical step for the development of reliable assays with clinical or research application in thrombosis and it will contribute to the field of nanomedicine in thrombosis.

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Deep vein thrombosis resolution is impaired in diet-induced type 2 diabetic mice

Abstract: Diet-induced type 2 diabetes may impair DVT resolution through altered inflammatory, fibrinolytic, and MMP responses.

Cited by 17 publications

References 45 publications

Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles

Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles

The Pathophysiology of Endothelial Function in Pregnancy and the Usefulness of Endothelial Markers

Physical Characterization of Mouse Deep Vein Thrombosis Derived Microparticles by Differential Filtration with Nanopore Filters

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