Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation

Cohen, Zoe; Gonzales, Raoul; Davis-Gorman, Grace; Copeland, Jack G.; McDonagh, Paul F.

doi:10.1016/s0049-3848(02)00334-1

Cited by 62 publications

(54 citation statements)

References 15 publications

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“…33 Cohen et al have showed that the level of caspase 6 increased in the type 2 diabetic rats as compared to the lean controls. 34 Moreover, Ulusoy et al showed that the level of caspase 1 reduced in diabetes mellitus. 35 In line with the studies, the levels of caspase 1 and IL-1a, and IL-1b were determined to be higher in the diabetic group.…”

Section: Discussionmentioning

confidence: 99%

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

et al. 2015

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Background: Diabetic nephropathy is the most common cause of end-stage renal disease. Emerging evidences indicate that many mechanistic pathways including apoptosis play an important role in the pathogenesis and progression of macrovascular and microvascular complications of diabetes mellitus. The aim of the present study is to show the effects of grape seed extract (GSE) on oxidative stress and apoptosis in the kidney of streptozotocin-induced diabetic rats.

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Section: Discussionmentioning

confidence: 99%

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

et al. 2015

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“…Blood samples were added to K 2 EDTA-coated Vacutainer® (Becton Dickinson & Co., Franklin Lakes, New Jersey) collection tubes, the preferred anticoagulant, prior to hematological analysis. The Model 9018 CP analyzer (Serono Diagnostics, Allentown, PA, USA) was then used to measure the following hematological parameters: red blood cell count, hematocrit, platelet count, and total white blood cell (WBC) count; including automated differentials for monocytes, lymphocytes, and polymorphonuclear (PMN) cells (Cohen et al, 2002;Chen et al, 2003). The automated differential is a 3-part differential that is an electronic size-impedance-based analysis to identify the lymphocyte, PMN, and monocyte populations.…”

Section: White Blood Cell Count and Differentialmentioning

confidence: 99%

Reoxygenation stress on blood–brain barrier paracellular permeability and edema in the rat

Witt

Mark

Sandoval

et al. 2008

Microvascular Research

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The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1hr) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 hr time course in conjunction with paracellular permeability, grey matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14 C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6−18hr time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 hr reoxygenation time points; and the second increase at only the 24 hr time point). Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, & IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White bloodcell counts showed significant decreases in lymphocytes (10 min-3 hr), increases in monocytes (10 min-3 hr & 12 hr), and increases in polymorphonuclear cells (1hr & 3 hr). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.

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“…Activated platelets shed microparticles that mediate a number of processes involved in coagulation, platelet adhesion, angiogenesis, and vascular smooth muscle cell proliferation Italiano et al, 2010). The concentrations of circulating platelet-derived microparticles correlate with the severity of a number of cardiovascular diseases, including acute coronary syndrome (Mallat et al, 2000), atherosclerosis hypertension (Preston et al, 2003), peripheral artery disease (Zeiger et al, 2000;van der Zee et al, 2006), aortic valve stenosis (Diehl et al, 2008), metabolic syndrome (Diamant et al, 2002), and type II diabetes (Nomura et al, 1995;Cohen et al, 2002;Koga et al, 2006). Platelet-derived microparticles possess binding sites for coagulation factors FVa (Alberio et al, 2000), FVIIIa (Gilbert et al, 1991), and FIXa (Hoffman et al, 1992a).…”

Section: Introductionmentioning

confidence: 99%

Protease-Activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets

et al. 2013

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With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.

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Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation

Cited by 62 publications

References 15 publications

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

Reoxygenation stress on blood–brain barrier paracellular permeability and edema in the rat

Protease-Activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets

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