Thrombosis Research (THROMB RES)

Publications in this journal

• Article: Impact of antithrombin deficiency on efficacy of edoxaban and antithrombin-dependent anticoagulants, fondaparinux, enoxaparin, and heparin.

  Toshio Fukuda, Chikako Kamisato, Yuko Honda, Tadashi Matsushita, Tetsuhito Kojima, Taketoshi Furugohri, Yoshiyuki Morishima, Toshiro Shibano
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  ABSTRACT: INTRODUCTION: Oral factor Xa (FXa) inhibitors are a novel class of anticoagulants that, unlike heparins, are expected to demonstrate antithrombotic effects independent of plasma antithrombin (AT) concentrations. We utilized heterozygous AT-deficient (AT+/-) mice to determine the impact of AT deficiency on anticoagulant and antithrombotic effects of edoxaban, a direct FXa inhibitor, and compared with heparins (fondaparinux, enoxaparin, and unfractionated heparin [UHF]). MATERIALS AND METHODS: The effects of edoxaban and heparins on in vitro prothrombin time and activated partial thromboplastin time were measured in plasma obtained from wild type (AT+/+) and AT+/- male mice. To assess the antithrombotic effects of these anticoagulants in vivo, venous thrombosis was induced in the inferior vena cava by FeCl3 treatment. Potency ratios of antithrombotic effects in AT+/- compared with AT+/+ mice were analyzed by a parallel line assay. RESULTS: In vitro studies demonstrated that the clotting-time prolongation effects of edoxaban were not affected by heterozygous AT deficiency whereas those of AT-dependent anticoagulants were attenuated. In AT+/- mice, the antithrombotic effects of AT-dependent anticoagulants were less potent than those in AT+/+ mice. In contrast, edoxaban was equipotent in preventing thrombus formation in both wild-type and AT-deficient mice. The attenuated antithrombotic effects of fondaparinux, enoxaparin, and UFH in AT-deficient mice were restored by AT supplementation. Edoxaban exerts a comparable antithrombotic effect even in mice with low plasma AT antigen and activity to that in wild-type mice. CONCLUSION: Edoxaban may potentially be prioritized over AT-dependent anticoagulants in patients with lower plasma AT concentration.
  Thrombosis Research 05/2013;
• Article: Histone induced platelet aggregation is inhibited by normal albumin.

  Fong W Lam, Miguel A Cruz, Hon-Chiu E Leung, Kathan S Parikh, C Wayne Smith, Rolando E Rumbaut
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  ABSTRACT: INTRODUCTION: Histones are small, nuclear proteins that serve to package DNA. Recent reports suggest that extracellular histones, including histone H4, may contribute to the pathogenesis of sepsis; they promote platelet aggregation and thrombosis when released into the circulation during inflammation or cell death. The mechanisms by which the body minimizes the deleterious effects of circulating histones are unclear. Because histones can bind to plasma proteins, including albumin, we hypothesized that normal albumin can prevent histones from activating platelets. MATERIALS AND METHODS: Platelets and platelet-free plasma were obtained from healthy, adult subjects. The dose-dependent effects of histone H4 on platelet aggregation were studied by optical aggregometry. The effects of native and albumin-depleted plasma (prepared by affinity chromatography) on histone-induced platelet aggregation were also assessed. The effects of normal and surface-neutralized albumin (through modification of carboxyl groups) on histone-induced platelet activation and aggregation were evaluated using flow cytometry and aggregometry. RESULTS: Histone H4 induced platelet aggregation in a dose-dependent manner. This histone-induced platelet aggregation was inhibited by both plasma and human serum albumin in a dose-dependent fashion. Furthermore, depletion of albumin from plasma reduced its ability to inhibit aggregation. Finally, surface neutralization of albumin decreased its ability to inhibit histone-induced activation and aggregation. DISCUSSION: These data suggest that normal albumin serves a role in preventing histone-induced platelet aggregation in a charge-dependent manner.
  Thrombosis Research 05/2013;
• Article: The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147) - a potential novel target in atherothrombosis prevention?

  Nader Joghetaei, Andreas Stein, Robert A Byrne, Christian Schulz, Lamin King, Andreas E May, Roland Schmidt
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  ABSTRACT: The immunoglobulin superfamily member EMMPRIN (CD147) plays an important role in a number of organ systems, including the cardiovascular system. Here we review the contemporary understanding of EMMPRIN and EMMPRIN-associated sequelae in the course of atherosclerosis. A significant body of data documents the pivotal role of EMMPRIN in the complex processes of atherogenesis, atheroprogression, and acute atherosclerothrombosis, a role that goes beyond that of a mere marker of inflammation.
  Thrombosis Research 05/2013;
• Article: Effectiveness of deep vein thrombosis screening on admission to a rehabilitation hospital: A prospective study in 1043 consecutive patients.

  Masanori Wada, Masayuki Iizuka, Yasuo Iwadate, Iwao Yamakami, Katsunori Yoshinaga, Naokatsu Saeki
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  ABSTRACT: INTRODUCTION: The diagnosis and treatment of deep vein thrombosis/pulmonary embolism (DVT/PE) are important issues not only in acute-care hospitals, but also in rehabilitation hospitals. To test the hypothesis that DVT/PE occurring at rehabilitation hospitals is carried over from acute-care hospitals, we evaluated a method of DVT screening on admission that combined D-dimer (D-D) measurement and compression ultrasound (CUS). MATERIAL AND METHODS: This prospective single-center observational study included 1043 patients who were admitted to our rehabilitation hospital between August 1, 2007, and August 1, 2011, after excluding those meeting the exclusion criteria. We screened patients on admission and observed the occurrence of DVT/PE until discharge. RESULTS: Of the 1043 patients, 152 (14.6%) had a D-D level of ≥3.0μg/mL on admission. CUS was performed for these patients and indicated the presence of DVT in 15 patients (1.4%), who were subsequently treated. Of these 15 patients, six (40%) had no DVT symptoms, and five of these six patients had spinal cord injury. Of 137 patients who were CUS negative, two developed DVT/PE within 8days of hospitalization, and recovery was achieved by treatment. No subsequent occurrence was observed. CONCLUSIONS: These results indicated all cases were carried over from acute-care hospitals. Six out of 15 patients had no symptoms of DVT/PE. Thus, this method of DVT screening on admission to a rehabilitation hospital is useful for risk management.
  Thrombosis Research 05/2013;
• Article: In Vitro Effects of Recombinant Activated Factor VII on Thrombin Generation and Coagulation Following Inhibition of Platelet Procoagulant Activity by Prasugrel.

  Michael Mazzeffi, Fania Szlam, Joseph A Jakubowski, Kenichi A Tanaka, Atsuhiro Sugidachi, Jerrold H Levy
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  ABSTRACT: INTRODUCTION: Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about its effects on thrombin generation or what strategies may emergently reverse its anticoagulant effects. In the current study we evaluated whether recombinant activated factor VII may reverse prasugrel induced effects and increase thrombin generation in an in vitro model. METHODS: The effect of prasugrel active metabolite, PAM (R-138727), was evaluated on platelet aggregation, thrombin generation, and rotational thromboelastometry parameters using blood from 20 healthy volunteers. Additionally, we evaluated the effects of adenosine diphosphate (ADP) and recombinant activated factor VII on restoring these parameters towards baseline values. RESULTS: PAM reduced maximum platelet aggregation and led to platelet disaggregation. It also decreased peak thrombin, increased lag time, and increased time to peak thrombin. Treatment with recombinant activated factor VII restored all three parameters of thrombin generation towards baseline. ADP decreased lag time and time to peak thrombin, but had no effect on peak thrombin. When recombinant activated factor VII and ADP were combined they had a greater effect on thrombin parameters than either drug alone. PAM also increased thromboelastometric clotting time and clot formation time, but had no effect on maximum clot firmness. Treatment with either recombinant activated factor VII or ADP restored these values towards baseline. CONCLUSIONS: Recombinant activated factor VII restores thrombin generation in the presence of PAM. In patients taking prasugrel with life-threatening refractory bleeding it has the potential to be a useful therapeutic approach. Additional clinical studies are needed to validate our findings.
  Thrombosis Research 05/2013;
• Article: Dabigatran in clinical practice - One-year experience at Skåne University Hospital.

  Elin Bergman, J Gustav Smith, Mattias Wieloch, Oscar Ö Braun, Peter Svensson, Jesper van der Pals
  Thrombosis Research 05/2013;
• Article: Serum des-R prothrombin activation peptide fragment 2: A novel prognostic marker for disseminated intravascular coagulation.

  Soie Chung, Ji-Eun Kim, Hyun Kyung Kim, Eun Hee Yeon, Yong Sung Shin, Chul Woo Kim
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  ABSTRACT: INTRODUCTION: Disseminated intravascular coagulation (DIC) is diagnosed based on the combination of predisposing underlying conditions and laboratory tests for plasma coagulation markers. Because the collection of blood plasma samples is a fastidious procedure, the serum sample method may be preferred for measurement of coagulation markers when feasible. MATERIALS AND METHODS: The novel serum marker des-R prothrombin activation peptide fragment 2 (des-R F2) was measured using a sandwich enzyme-linked immunosorbent assay in 181 patients suspected of having DIC. Thrombin generation potential was estimated with a calibrated automated thrombogram. RESULTS: Serum des-R F2 was generated with an in vitro clotting process within a serum separation tube after blood collection. Carboxypeptidase inhibitor inhibited the formation of des-R F2 during in vitro clotting. Low levels of prothrombin and thrombin generation potential resulted in low serum des-R F2 levels. Serum des-R F2 was significantly decreased in overt DIC. Levels of des-R F2 correlated with DIC severity and other coagulation markers. Of note, the decrease in serum des-R F2 levels was a significant marker for predicting mortality. CONCLUSIONS: The serum marker, des-R F2, can be used for the investigation of DIC severity and prognosis. It should be considered a useful marker, especially when only serum samples are available.
  Thrombosis Research 05/2013;
• Article: Effective, selective and specific inhibition of COX-1 may overcome the "aspirin paradox"

  Frederick A Ofosu
  Thrombosis Research 05/2013;
• Article: Six novel missense mutations causing factor X deficiency and application of thrombin generation test.

  Qian Liang, Qiong Chen, Qiulan Ding, Fang Wu, Xuefeng Wang, Xiaodong Xi, Hongli Wang
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  ABSTRACT: INTRODUCTION: Inherited factor X (FX) deficiency is a rare hemorrhagic condition characterized by a variable clinical presentation weakly correlating with laboratory phenotype and genotype. Thrombin generation test (TGT) offers potential clinical advantages in the evaluation of hypocoagulable states. MATERIALS AND METHODS: Five FX assays were performed using clotting, chromogenic and immunological methods. The factor X gene (F10) defects were analyzed by direct sequencing. Thrombin generation (TG) was measured using a standard procedure with commercial reagents at 1pM and 5pM of tissue factor (TF). The influence of contact activation on TG at the two TF concentrations was analyzed by the addition of corn trypsin inhibitor (CTI). RESULTS: Seven missense mutations were identified in the F10 of the four probands with FX deficiency, six of which (Ser425Pro, Ala-29Pro, Phe324Leu, Ala235Thr, Cys111Arg and Met362Thr) were novel and associated with type I FX deficiency. TG measurements at 1pM TF need the addition of CTI in both healthy individuals and FX-deficient patients. TG parameters of ETP, Peak and Rate correlated well with the FX:C levels and the clinical expressions of the FX-deficient patients at 1pM TF with CTI. There is a higher sensitivity for FX deficiency at 1pM TF compared with 5pM TF in FX-deficient patients. CONCLUSIONS: TGT may serve as a useful laboratory tool to assess the individual clinical manifestation of the patients with FX deficiency and 1pM TF concentration in the presence of CTI is recommended.
  Thrombosis Research 05/2013;
• Article: Histone deacetylase inhibitors reduce glycoprotein VI expression and platelet responses to collagen related peptide.

  Mark J Bishton, Elizabeth E Gardiner, Simon J Harrison, H Miles Prince, Ricky W Johnstone
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  ABSTRACT: INTRODUCTION: Platelet Glycoprotein (GP)VI is a member of the immunoglobulin superfamily expressed only on platelets, and is the major signalling receptor for collagen. Histone deacetylase inhibitors (HDACi) are anti-cancer agents used for the treatment of haematological malignancies, and we examined the effects of administration of HDACi to mice on platelet function including responses to agonists including collagen related peptide (CRP). MATERIALS AND METHODS: C57BL/6 mice were injected with two structurally different HDACi, panobinostat and romidepsin, for three days and platelet receptor levels and responses to agonists were assessed by flow cytometry and western blot. RESULTS: Platelets from mice treated with either HDACi were impaired in their ability to respond to CRP, but not thrombin or adenosine diphosphate (ADP). HDACi treatment increased acetylation of megakaryocytic GPVI, resulting in loss of intact (~60-65-kDa) GPVI and formation of ~10-kDa remnant GPVI. Circulating platelets had reduced surface and total expression of GPVI. Platelets from mice treated with HDACi had impaired GPVI signalling following treatment with CRP, resulting in inhibition of Syk phosphorylation and activation, and the final common pathways of platelet activation. CONCLUSIONS: Administration of HDACi in vivo may ablate platelet responses to agonists and platelet function.
  Thrombosis Research 05/2013;
• Article: Shiga toxin downregulates tissue factor pathway inhibitor, modulating an increase in the expression of functional tissue factor on endothelium.

  Eric F Grabowski, Rafail I Kushak, Bohan Liu, Julie R Ingelfinger
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  ABSTRACT: INTRODUCTION: Endothelial expression of tissue factor (TF) may play a major role in (Stx)-related hemolytic uremic syndrome. We examined human umbilical vein endothelial cell (HUVEC) monolayers to determine the interaction between TF and TF pathway inhibitor (TFPI), hypothesizing that changes in TFPI modulate TF expression. MATERIALS AND METHODS: We studied 1) cell surface expression of globotriasylceramide (Gb3, the receptor for Stx) with Stx-1 (10 pM), TNFα (20Ng/ml), or Stx-1 plus TNFα compared to control, 2) gene expression of TF and TFPI, 3) total cellular and cell surface antigenic TF and TFPI, 4) TFPI secretion into supernatant, and 5) factor Xa production. RESULTS AND CONCLUSIONS: Gb3 expression, negligible with control and Stx-1 alone, increased significantly with TNFα and with Stx-1 plus TNFα. TF mRNA increased 1.25±0.32- fold (N=9; p=0.041) with Stx-1 alone vs. 2.82±0.92-fold (N=13; p<0.0005) with TNFα alone. However, Stx-1 plus TNFα yielded a 6.51±3.48-fold increase (N=17; p<0.0005). TFPI mRNA decreased with TNFα (p<0.001) and Stx-1 plus TNFα (p<0.0005). Total cellular and cell surface TF antigen increased significantly with TNFα, but no further with Stx-1 plus TNFα. Total TFPI cellular and cell surface antigen levels, and TFPI secretion decreased significantly with Stx-1 plus TNFα. Median factor Xa production for Stx-1 plus TNFα vs TNFα alone increased (p<0.001) 3.24-fold. Our results indicate that a subinhibitory concentration of Stx-1 plus TNFα impairs TFPI gene expression, synthesis, cell-surface association, and secretion, leading to augmented functional TF.
  Thrombosis Research 05/2013;
• Article: Does plexin-B1, a semaphorin 4D receptor, play a role in thrombosis?

  Eileen Bird, Patricia L Smith, Dietmar Seiffert, George C Psaltis, Jinwen Huang, William A Schumacher
  Thrombosis Research 04/2013;
• Article: Hydrodynamic characterization of recombinant human fibrinogen species.

  Bertrand Raynal, Barbara Cardinali, Jos Grimbergen, Aldo Profumo, Susan T Lord, Patrick England, Mattia Rocco
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  ABSTRACT: INTRODUCTION: Fibrinogen is a key component of the blood coagulation system and plays important, diverse roles in several relevant pathologies such as thrombosis, hemorrhage, and cancer. It is a large glycoprotein whose three-dimensional molecular structure is not fully known. Furthermore, circulating fibrinogen is highly heterogeneous, mainly due to proteolytic degradation and alternative mRNA processing. Recombinant production of human fibrinogen allows investigating the impact on the three-dimensional structure of specific changes in the primary structure. METHODS: We performed analytical ultracentrifugation analyses of a full-length recombinant human fibrinogen, its counterpart purified from human plasma, and a recombinant human fibrinogen with both Aα chains truncated at amino acid 251, thus missing their last 359 amino acid residues. RESULTS: We have accurately determined the translational diffusion and sedimentation coefficients (Dt(20,w)(0), s(20,w)(0)) of all three species. This was confirmed by derived molecular weights within 1% for the full length species, and 5% for the truncated species, as assessed by comparison with SDS-PAGE/Western blot analyses and primary structure data. No significant differences in the values of Dt(20,w)(0) and s(20,w)(0) were found between the recombinant and purified full length human fibrinogens, while slightly lower and higher values, respectively, resulted for the recombinant truncated human fibrinogen compared to a previously characterized purified human fibrinogen fragment X obtained by plasmin digestion. CONCLUSIONS: Full-length recombinant fibrinogen is less polydisperse but hydrodynamically indistinguishable from its counterpart purified from human plasma. Recombinant Aα251-truncated human fibrinogen instead behaves differently from fragment X, suggesting a role for the Bβ residues 1-52 in inter-molecular interactions. Overall, these new hydrodynamic data will constitute a reliable benchmark against which models of fibrinogen species could be compared.
  Thrombosis Research 04/2013;
• Article: Acute cytomegalovirus infection as a transient risk factor for thrombosis: Report of three cases and focus on specific coagulation pathways.

  Marie Pichenot, Sandrine Morell-Dubois, Clara Flateau, Laurène Deconinck, Pierre-Yves Hatron, Marc Lambert
  Thrombosis Research 04/2013;
• Article: Response to antiplatelet therapy is independent of endogenous thrombin generation potential.

  Thomas Gremmel, Simon Panzer, Sabine Steiner, Daniela Seidinger, Renate Koppensteiner, Ingrid Pabinger, Christoph W Kopp, Cihan Ay
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  ABSTRACT: BACKGROUND: Thrombin is the most potent platelet activator, and achieves rapid platelet activation even in the presence of antiplatelet therapy. Since activated platelets respond stronger to additional stimuli, the extent of endogenous thrombin generation may in part be responsible for the reported response variability to aspirin and clopidogrel therapy. PATIENTS AND METHODS: Thrombin generation potential was measured with a commercially available assay, and platelet reactivity was assessed with the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, light transmission aggregometry (LTA), the VerifyNow aspirin and P2Y12 assays, and multiple electrode aggregometry (MEA) in 316 patients on dual antiplatelet therapy undergoing angioplasty and stenting. RESULTS: Peak thrombin, the lag phase and the area under the curve of thrombin generation correlated poorly with on-treatment platelet reactivity by all test systems. High on-treatment residual platelet reactivity (HRPR) in response to arachidonic acid was seen in 33 (10.5%), 41 (13%), and 79 (25.7%) patients by LTA, the VerifyNow aspirin assay, and MEA, respectively. HRPR in response to adenosine diphosphate was seen in 150 (48.1%), 48 (15.3%), 106 (33.7%), and 118 (38.3%) patients by the VASP assay, LTA, the VerifyNow P2Y12 assay, and MEA, respectively. Peak thrombin generation did not differ between patients without and with HRPR by the VASP assay, LTA, the VerifyNow P2Y12 assay and MEA. In the VerifyNow aspirin assay, patients without HRPR had higher peak thrombin generation than patients with HRPR (p=0.01). Finally, patients without and with high peak thrombin generation exhibited similar on-treatment platelet reactivity by all test systems, and high peak thrombin generation occurred to a similar extent in patients without and with HRPR. CONCLUSION: Response to antiplatelet therapy with aspirin and clopidogrel is not associated with thrombin generation potential.
  Thrombosis Research 04/2013;
• Article: Human platelets do not express tissue factor.

  Bjarne Osterud, Jan Ole Olsen
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  ABSTRACT: BACKGROUND: The controversy about the expression of tissue factor (TF) in platelet after de novo synthesis prevail despite many groups recognize that platelet isolation, assays and reagents, particularly non-specific antibodies, may account for the diversity. In this study the potential of TF expression was evaluated using immune-purified human platelets and employing a very sensitive and highly specific TF activity assay. METHODS: Isolated platelets in plasma anti-coagulated with Fragmin were subjected to stimulation by LPS plus PMA, IgG antibody or TRAP and tested for TF activity. RESULTS: Platelets stimulated with LPS plus PMA for 4hours expressed trace amounts of TF like activity (PCA), not inhibited by anti-TF antibody (0.2±0.1mU/ml blood). Platelets, not immune-adsorbed to remove monocytes, showed significant TF activity (2.0±0.9mU/ml blood) that was nearly abolished by anti-TF antibody. IgG antibody from patient with lupus anticoagulant failed to enhance the trace amount of PCA as compared to the control in contrast to high TF activity induced in monocytes (0.4±0.1mU/ml blood versus 27.5±10.5mU/10(6) cells) showing that activation of complement is not mediating TF expression. Platelet subjected to TRAP activation for 10min possessed only trace amounts of PCA that was not inhibited by anti-TF antibody and slightly enhanced by anti-TFPI antibody. CONCLUSIONS: It is concluded that platelets free of monocytes do not express TF activity when stimulated by LPS or activated complement factors, implying no role for Toll like receptor (TLR4) as suggested recently. There is no evidence of TF activity associated with platelets as a result of rapid and dynamic process.
  Thrombosis Research 04/2013;
• Article: Cilostazol for peripheral arterial disease could reduce stroke risk?

  A Watson, D P Mikhailidis, G Stansby
  Thrombosis Research 04/2013;
• Article: The isolation of fibrinogen monomer dramatically influences fibrin polymerization.

  Lihong Huang, Susan T Lord
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  ABSTRACT: Fibrin polymerization begins with the thrombin-catalyzed cleavage of fibrinopeptides from fibrinogen and proceeds through several assembly steps to form an insoluble fibrin clot. Using dynamic light scattering (DLS), we found that purified fibrinogens are polydisperse, containing small amounts of fibrinogen complexes. In order to characterize the impact of these complexes, we used gel filtration chromatography to isolate monomers from three fibrinogens: plasma, recombinant, and recombinant variant Aα251. SDS-PAGE analysis showed that the polypeptides in the monomers were indistinguishable from those in the initial fibrinogen. DLS showed the fibrinogen monomers were monodisperse. We used turbidity to follow polymerization and found the polymerization of fibrinogen monomers was markedly different from the polymerization of the initial fibrinogen; the final optical density (OD) was significantly higher for monomers. Moreover, the polymerization curve for fibrinogen monomers was independent of the polymerization curves of the fibrinogen samples without gel filtration. For example, monomers isolated from two recombinant fibrinogen preparations polymerized similarly even though the final OD increased 2-fold for one preparation and 3-fold for the other. Scanning electron microscopy of the fibrin clots verified the turbidity data; monomer clots had thicker fibers. We conclude that fibrinogen complexes alter the kinetics of polymerization and impair the assembly of monomers into protofibrils and fibers.
  Thrombosis Research 04/2013;
• Article: Allogeneic bone marrow mesenchymal stem cells transplantation for stabilizing and repairing of atherosclerotic ruptured plaque.

  Shun-Miao Fang, Da-Yong Du, Yun-Tian Li, Xing-Li Ge, Peng-Tao Qin, Qing-Hua Zhang, Yang Liu
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  ABSTRACT: INTRODUCTION: There have been no satisfactory therapies on stabilizing and repairing ruptured plagues nowadays, which are the fundamental causes of acute coronary syndrome (ACS) and stroke. The aim of this study was to investigate the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in stabilizing and repairing ruptured plaques. MATERIALS AND METHODS: 28 male New Zealand rabbits were randomly divided into 2 groups after establishment of atherosclerotic disrupted plaque model by liquid nitrogen frostbite: MSCs transplantation group and control group. MSCs were isolated, cultured in vitro, and labeled with BrdU. BrdU-incorporated MSCs (MSCs transplantation group) or an equal amount of IMDM medium without MSCs (control group) were transplanted into vessels with ruptured plaque. PAI-1, MMP-9 and hs-CRP were determined by ELISA of blood 3days and 4weeks after transplantation. Rabbits were sacrificed 4weeks after transplantation and plaque repair was assessed by HE and Masson's trichrome staining. Transplanted BrdU-positive cells were identified by immunohistochemistry. RESULTS: Four weeks after MSCs transplantation, PAI-1, MMP-9 and hs-CRP were reduced significantly in all experimental animals (p<0.001). The reduction was more evident in the transplantation group than in the control group (p<0.01). In addition, the transplantation group showed dramatically higher numbers of newly formed endothelial cells, collagen fibers, and proliferative BrdU-positive cells at plaque areas. CONCLUSION: This study demonstrates that allogeneic MSCs transplantation can stabilize and repair ruptured plaques, which represents a novel approach for ACS and stroke.
  Thrombosis Research 04/2013;