Publications (31)116.12 Total impact
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Article: Atrial fibrillation in pigs induces left atrial endocardial transcriptional remodelling.
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ABSTRACT: The leading cause of cardioembolic stroke is atrial fibrillation (AF), which predisposes to atrial thrombus formation. Although rheological alterations promote a hypercoagulable environment, as yet undefined factors contribute to thrombogenesis. The role of the endocardium has barely been explored. To approach this topic, rapid atrial pacing (RAP) was applied in four pigs to mimic AF. Left and right endocardial cells were isolated separately and their gene expression pattern was compared with that of four control pigs. The AF-characteristic rhythm disorders and endothelial nitric oxide synthase down-regulation were successfully reproduced, and validated RAP to mimic AF. A change was observed in the transcriptomic endocardial profile after RAP: the expression of 364 genes was significantly altered (p<0.01), 29 of them having passed the B>0 criteria. The left atrial endocardium [325 genes (7 genes, B>0)] was largely responsible for such alterations. Blood coagulation, blood vessel morphogenesis and inflammatory response are among the most significant altered functions, and help to explain the activation of coagulation observed after RAP: D-dimer, 0.49 (1.63) vs. 0.23 (0.24) mg/l [median (interquartile range)] in controls, p=0.02. Furthermore, three genes directly related to thrombotic processes were differentially expressed after RAP: FGL2 [fold change (FC)=0.85; p=0.007], APLP2 (FC=-0.47; p=0.005) and ADAMTS-18 (FC=-0.69; p=0.004). We demonstrate for the first time that AF induces a global expression change in the left atrial endocardium associated with an activation of blood coagulation. The nature of some of the altered functions and genes provides clues to identify new therapeutic targets.Thrombosis and Haemostasis 07/2012; 108(4):742-9. · 5.04 Impact Factor -
Article: Activated protein C: reasons to believe.
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ABSTRACT: The old axiom "one protein, one function" no longer holds true. Activated protein C (APC), the serine protease which plays a central role in anticoagulation, has gained attention due to its unsuspected (until a decade ago) ability to promote cell signaling mechanisms leading to cell/tissue protection. Since the PROWESS clinical trial initially pointed at APC as the only drug able to reduce the mortality associated with severe sepsis [1], many studies in animal models have demonstrated that APC shows promise in a variety of pathologies. Diabetic nephropathy, inflammatory bowel disease, systemic lupus erythematosus, amyotrophic lateral sclerosis (ALS), cancer metastasis and ischemic stroke are among the conditions that APC could help to fight against, thanks to its antiadhesive, antiapoptotic or barrier enhancement abilities [2]. © 2012 International Society on Thrombosis and Haemostasis.Journal of Thrombosis and Haemostasis 07/2012; 10(9):1733-5. · 5.73 Impact Factor -
Article: Is EPCR a multi-ligand receptor? Pros and cons.
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ABSTRACT: In the last decade, the endothelial cell protein C/activated protein C receptor (EPCR) has received considerable attention. The role initially attributed to EPCR, i.e. the enhancement of protein C (PC) activation by the thrombin-thrombomodulin complex on the surface of the large vessels, although important, did not go beyond the haemostasis scenario. However, the discovery of the cytoprotective, anti-inflammatory and anti-apoptotic features of the activated PC (APC) and the required involvement of EPCR for APC to exert such actions did place the receptor in a privileged position in the crosstalk between coagulation and inflammation. The last five years have shown that PC/APC are not the only molecules able to interact with EPCR. Factor VII/VIIa (FVII/VIIa) and factor Xa (FXa), two other serine proteases that play a central role in haemostasis and are also involved in signalling processes influencing wound healing, tissue remodelling, inflammation or metastasis, have been reported to bind to EPCR. These observations have paved the way for an exploration of unsuspected new roles for the receptor. This review aims to offer a new image of EPCR in the light of its extended panel of ligands. A brief update of what is known about the APC-evoked EPCR-dependent cell signalling mechanisms is provided, but special care has been taken to assemble all the information available about the interaction of EPCR with FVII/VIIa and FXa.Thrombosis and Haemostasis 02/2012; 107(5):815-26. · 5.04 Impact Factor -
Article: Factor X and factor VII binding to endothelial protein C receptor differs between species.
Journal of Thrombosis and Haemostasis 06/2011; 9(6):1255-7. · 5.73 Impact Factor -
Article: Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo.
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ABSTRACT: The endothelial protein C receptor (EPCR) plays an anticoagulant role by improving protein C activation. Although low levels of activated protein C (APC) constitute a thrombosis risk factor, the relationship between modulating EPCR function and thrombosis has not been addressed so far. Monoclonal antibodies (mAb) against murine EPCR were raised, and their ability to block protein C/APC binding was tested. The ferric chloride carotid artery injury model in mice was chosen to test the effect of anti-EPCR mAb on thrombus formation. The time to total occlusion of the vessel was analysed in three groups, given an isotype control mAb (IC), a blocking (RCR-16) or a non-blocking (RCR-20) anti-EPCR mAb. RCR-16 prevented the interaction between protein C/APC and EPCR as demonstrated by surface plasmon resonance and flow cytometry, and inhibited the activation of protein C on the endothelium. IC and RCR-20 were unable to induce such effects. In vivo , RCR-16 shortened the time to total vessel occlusion with respect to IC [13.4 +/- 1.0 (mean +/- SD) and 17.8 +/- 3.2 minutes, respectively, p<0.001]. Occlusive thrombi lasting for more than one hour were observed in all RCR-16-treated animals, but only in 43% of IC-treated ones. Results with RCR-20 were indistinguishable from those observed with IC. For the first time, a direct relationship between blocking EPCR and thrombosis is demonstrated. Blocking anti-EPCR autoantibodies can predispose to thrombosis episodes and may constitute a new therapeutic target.Thrombosis and Haemostasis 03/2010; 103(6):1239-44. · 5.04 Impact Factor -
Article: Binding of factor VIIa to the endothelial cell protein C receptor reduces its coagulant activity.
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ABSTRACT: Endothelial cell protein C receptor (EPCR) binds protein C through its gamma-carboxyglutamic acid (Gla) domain and enhances its thrombin-thrombomodulin complex-dependent activation. So far, only protein C/activated protein C has been shown to interact with EPCR. Factor VII (FVII), the coagulation trigger upon tissue factor (TF) interaction, is a serine protease whose Gla domain is highly homologous to the Gla domain of protein C. To characterize the binding of FVII/FVIIa to EPCR and its functional consequences. We demonstrated by surface plasmon resonance (SPR) that FVII/FVIIa binds to EPCR through its Gla domain. At therapeutic concentrations, FVIIa reduced the activation of protein C by 40%. Soluble EPCR (sEPCR) was also able to prolong dose-dependently the clotting time induced by the FVIIa-TF complex. SPR and amidolytic experiments showed that FVIIa is able to interact simultaneously with TF and EPCR, thus ruling out the possibility that the effect of EPCR on clotting time was due to the inhibition of the binding between FVIIa and TF. sEPCR inhibited dose-dependently the activation of FX by the FVIIa-TF complex. Notably, blocking the binding site of EPCR on the endothelial surface increased the generation of FXa 2-fold. EPCR binds to FVII/FVIIa and inhibits the procoagulant activity of the FVIIa-TF complex.Journal of Thrombosis and Haemostasis 10/2007; 5(9):1817-24. · 5.73 Impact Factor -
Article: Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis.
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ABSTRACT: The endothelial protein C receptor (EPCR) binds protein C and enhances its activation. Anti-EPCR autoantibodies are found in patients with antiphospholipid syndrome and may explain the increased risk of thrombosis in these patients. Anti-EPCR autoantibodies have been associated with fetal death and myocardial infarction in young women. To determine whether anti-EPCR autoantibodies are associated with deep vein thrombosis (DVT). We measured plasma anti-EPCR autoantibody levels in the Leiden Thrombophilia Study (LETS), a population-based case-control study consisting of 474 patients with a first DVT and 474 control subjects. The estimated risk of DVT was increased approximately 2-fold in the presence of elevated IgA, IgG or IgM anti-EPCR autoantibodies (i.e. levels above the 90th percentile as measured in the control subjects). The risk conferred by anti-EPCR increased in a dose-dependent manner for IgA and IgG. When anti-EPCR autoantibodies were considered in the co-presence of lupus anticoagulant (LAC) the odds ratio (OR) was 6.1 [95% CI 1.3-27.9]. Anti-EPCR without LAC remained associated with DVT (OR 1.6; 95% CI 1.2-2.1). Anti-EPCR autoantibodies were associated with high levels of D-dimer and soluble EPCR in controls, suggestive of a prothrombotic status induced by the autoantibodies. This study demonstrates that the presence of anti-EPCR autoantibodies is a moderate risk factor for DVT in the general population.Journal of Thrombosis and Haemostasis 08/2007; 5(7):1449-54. · 5.73 Impact Factor -
Article: Association of increased fibrinogen concentration with impaired activation of anticoagulant protein C.
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ABSTRACT: Low levels of activated protein C (APC) are a risk factor for venous thrombosis. The mechanisms leading to interindividual differences in APC are not totally elucidated. Protein C is activated by the thrombin-thrombomodulin complex. As thrombin binds to fibrinogen and thrombomodulin through a common region, it is conceivable that fibrinogen influences the activation of protein C. This would help to explain the association between high levels of fibrinogen and an increased thrombotic risk. We analyzed the association between circulating APC levels and fibrinogen concentration in 382 healthy subjects. Subsequently, we studied the effect of increasing fibrinogen concentrations on the APC generation on cultured endothelial cells. An independent inverse association between circulating APC levels and fibrinogen was found [betacoefficient, -0.16; 95% confidence interval (95% CI) -0.26, -0.06; P = 0.001]. For each 100 mg dL(-1) increase in fibrinogen, the independent risk of having low APC levels (<0.7 ng mL(-1)) was almost three times higher (OR 2.8; 95% CI 1.1, 7.2; P = 0.04). Accordingly, a notable association between increasing fibrinogen concentrations and the reduction in the thrombin-thrombomodulin dependent activation of protein C on endothelial cells was found (r = -0.57; P = 0.002). We present evidence of an inverse association between circulating APC and fibrinogen levels. According to this finding together with the results of our in vitro experiments, we propose that the impairment in the generation of APC on endothelial cells constitutes a new prothrombotic mechanism of fibrinogen.Journal of Thrombosis and Haemostasis 03/2006; 4(2):398-402. · 5.73 Impact Factor -
Article: Autoantibodies against the endothelial receptor of protein C are associated with acute myocardial infarction in young women.
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ABSTRACT: Acute myocardial infarction (AMI) is rare among young women. The search for unknown risk factors is warranted. Endothelial protein C receptor (EPCR) is largely present at the endothelial surface of large arteries. No studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are available. Plasma IgA, IgM and IgG anti-EPCR levels were measured by enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived a first AMI and 165 healthy women, matched by age and geographical origin. Using the 90th percentile of IgA anti-EPCR in the control group, IgA anti-EPCR were independently associated with AMI after adjustment for cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant increase in the risk was found when women above the 90th percentile were compared with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti-EPCR were similar in patients and controls. A total of 145 patients underwent coronary arteriography. IgA or IgM anti-EPCR were not different among patients with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24, respectively). High levels of IgA and, to a lesser extent, IgM anti-EPCR, are associated with AMI in young women.Journal of Thrombosis and Haemostasis 08/2005; 3(7):1454-8. · 5.73 Impact Factor -
Article: Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF).
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ABSTRACT: Endothelial damage plays a central role in the development of an SIRS-related Multiple Organ Dysfunction Syndrome (MODS) as a consequence of the establishment of a hemostatic imbalance between coagulation and fibrinolysis systems. Until now, sepsis is the SIRS model that has been most studied. The aim of this study was to assess the endothelial damage and the hemostatic imbalance in early stages of an SIRS of different origins, and to study if there are any differences in these disturbances between infectious and noninfectious SIRS. The endothelial damage and hemostatic changes were studied in 40 patients with SIRS (with less than 12 h of evolution) and an acute renal failure. Infectious SIRS was diagnosed in 19 cases and noninfectious SIRS in the remaining 21 patients. Patients with SIRS presented significantly higher values (p<0.001) for factors related to endothelial damage [von Willebrand factor (vWF), thrombomodulin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) antigen], hypercoagulability [prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT)], and fibrinolysis (D-dimer and PAI activity) with respect to the control group. However, although the group with infectious SIRS presented higher values for all the factors except for the t-PA and D-dimer with respect to SIRS of other origins, none of these differences reached statistical significance (p>0.05). Our data show that patients with SIRS and associated acute renal failure, irrespective of the origin (infectious or noninfectious), show signs of intense endothelial damage and hypercoagulability throughout the process.Thrombosis Research 11/2000; 100(1):19-25. · 2.44 Impact Factor -
Article: Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis.
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ABSTRACT: We compared the efficacy and safety of low molecular weight heparins (LMWH) and unfractionated heparin (UFH) in the treatement of deep venous thrombosis (DVT). A comparison between two daily subcutaneous injections of LMWH against a single injection was also performed. The study was performed by a meta-analysis. Clot improvement in venography, recurrency, total mortality and major hemorrhages were assessed in 4,472 patients with DVT from 21 studies treated with subcutaneous LMWH or UFH. An improvement in clot reduction (odds ratio 0.73, 95% confidence interval 0.59 to 0.90, p = 0.004), a decrease in total mortality (0. 68, 0.50 to 0.91, p = 0.012) and a lower incidence of hemorrhage (0. 65, 0.43 to 0.98, p = 0.047) were observed in LMWH treated patients. There were no differences in recurrences (0.78, 0.59 to 1.04, p = 0. 10). A single dose of LMWH was better than two in reducing major bleeding (c2 = 4.99, p = 0.025); however, the two dose regimen was more effective in clot reduction (c2 = 8.56, p = 0.004). LMWH is superior to UFH in terms of safety and efficacy. A single daily dose of LMWH dose is a suitable therapeutic regimen and could facilitate the outpatient treatment of venous thromboembolism.Haematologica 10/2000; 85(9):935-42. · 6.42 Impact Factor -
Article: Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1.
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ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.Thrombosis and Haemostasis 08/2000; 84(1):65-70. · 5.04 Impact Factor -
Article: [The role of PAI-1 in thrombotic events].
Medicina Clínica 07/1999; 113(2):63-9. · 1.38 Impact Factor -
Article: Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells.
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ABSTRACT: Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect.Thrombosis Research 06/1999; 94(3):137-45. · 2.44 Impact Factor -
Article: Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits.
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ABSTRACT: We evaluated the effect of r-hirudin and/or tissue-plasminogen activator (t-PA) in a model of DIC in rabbits induced by i.v. infusion of 100 micrograms/kg/h/6 h endotoxin. Rabbits were treated with saline (endotoxin control group), r-hirudin at 0.3 mg/kg/h/6 h, t-PA at 0.3 mg/kg for 90 min and r-hirudin plus t-PA at the doses described above. The best results were achieved when r-hirudin and t-PA were infused together. This treatment reduced the consumption of platelets and protein C and attenuated the increase of PAI-1 more efficiently than r-hirudin or t-PA alone. r-Hirudin plus t-PA also resulted in the lowest formation of fibrin deposits in the kidneys. Finally, mortality at 24 h dropped from 70% in the endotoxin control group to 40%, 10% and 0% in the t-PA, r-hirudin and r-hirudin plus t-PA groups respectively. None of the t-PA-infused rabbits which had died by 24 h showed macroscopic signs of haemorrhage. r-Hirudin alone was better than t-PA alone, as was shown by fibrin deposits and mortality. We conclude that r-hirudin and t-PA given simultaneously were more efficient than either given alone in this model of DIC. Effective thrombin inhibition, which could influence other pathophysiological mechanisms apart from coagulation, together with the improvement in fibrinolysis, would explain these results.British Journal of Haematology 05/1999; 105(1):117-21. · 4.94 Impact Factor -
Article: Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha.
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ABSTRACT: Vascular fibrinolysis, a major natural defense mechanism against thrombosis, is a highly regulated process. The aim of this study was to evaluate the effect of endotoxin, tumor necrosis factor-alpha (TNFalpha) and interleukin-1alpha (IL-1alpha), on the fibrinolytic potential of cultured human umbilical vein endothelial cells (HUVEC). Samples of stimulated conditioned media were collected over a period of 24 hours to determine: plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activity, PAI-1 mRNA, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. Similar changes were observed after endotoxin and cytokine stimulation: there was a significant increase of PAI activity (p<0.01), starting at 6 hours, which remained 24 hours after stimulation. PAI-1 mRNA also showed an important rise with these agents, although cytokines induced an earlier and more intense inhibitor response (up to 6-fold increase). PA activity increased significantly at 6 hours (p<0.01) to drop at 24 hours and was mainly related to the presence of u-PA. We conclude that endotoxin,+TNFalpha and IL-1alpha induce profound alterations in the fibrinolytic potential of HUVEC, characterized by an initial rise of activators (u-PA) followed by a strong increase of PAI-1. These changes may be of pathophysiologic significance for thrombosis and inflammatory reactions.Haematologica 04/1999; 84(4):306-11. · 6.42 Impact Factor -
Article: Effects of low molecular weight heparin, alone or combined with antithrombin III, on mortality, fibrin deposits and hemostatic parameters in endotoxin-induced disseminated intravascular coagulation in rabbits.
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ABSTRACT: The effect of low molecular weight heparin (LMWH) with or without antithrombin III (AT III) has been studied in a rabbit model of disseminated intravascular coagulation (DIC) induced by continuous infusion of 100 microg/kg/hr of Escherichia coli endotoxin for 6 hr. LMWH (5 and 10 IU/kg/hr/6 hr), alone or in combination with AT III (20 U/kg/hr/6 hr), or saline were administered simultaneously with endotoxin. Hemostatic markers at 0, 2, and 6 hr as well as kidney fibrin deposits and the mortality rate at 24 hr were determined. Rabbits receiving only endotoxin showed an impairment in hemostasis, as well as high kidney fibrin deposits and a high mortality rate. LMWH alone did not exert any effect. The simultaneous infusion of LMWH and AT III exerted a beneficial effect on the hemostatic markers and reduced the kidney fibrin deposits as well as the mortality rate in a LMWH dose-dependent manner. Fibrinogen and protein C consumption were significantly higher and renal fibrin deposits more intense in the rabbits that had died in the first 24 hr. There was also a significant positive correlation between kidney fibrin deposits and platelets, fibrinogen, and protein C consumption, taking the whole rabbit population. It is concluded that the simultaneous infusion of LMWH and AT III is useful in this DIC model and would make it possible to reduce significantly the AT III doses used when AT III is given alone.American Journal of Hematology 02/1999; 60(1):6-11. · 4.67 Impact Factor -
Article: Acute generalized, widespread bleeding. Diagnosis and management.
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ABSTRACT: Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are required.Haematologica 12/1998; 83(11):1024-37. · 6.42 Impact Factor -
Article: Prevalence of FVR506Q and prothrombin 20210A mutations in the Navarrese population.
Thrombosis and Haemostasis 10/1998; 80(3):522-3. · 5.04 Impact Factor -
Article: Long-term cardiac rehabilitation program favorably influences fibrinolysis and lipid concentrations in acute myocardial infarction.
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ABSTRACT: The control of well-known atherosclerotic risk factors represents the optimal strategy in the prevention of acute coronary syndromes. It was the aim of this work to analyze the effects of a long-term cardiac rehabilitation program on the changes of fibrinolysis parameters and plasma lipid profile in coronary patients. The study was carried out in 30 (M/F:22/8, mean age 47 years) survivors of a first acute myocardial infarction (AMI) and in 30 healthy controls who underwent a cardiac rehabilitation program (9 months duration). Samples were taken before, at 3 and 9 months after the beginning of the program to measure: tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI-1) activity and antigen. A lipid profile including cholesterol (both HDL and LDL) and lipoprotein(a) was also assessed. The Wilcoxon and Mann-Whitney tests were used for statistical comparisons. There was a marked decrease of functional PAI-1 after 3 and 9 months as compared with baseline in AMI patients (p < 0.01). Results showed a significant increase of HDL-cholesterol (p < 0.01) and decrease of lipoprotein(a) levels after the exercise program (p < 0.01). The cardiac rehabilitation program improved fibrinolysis, by reducing the functional levels of PAI-1, and ameliorated the lipid profile by decreasing lipoprotein(a) and increasing HDL-cholesterol in patients with AMI. A long-term cardiac rehabilitation has positive effects on some risk factors for coronary disease.Haematologica 06/1998; 83(6):519-24. · 6.42 Impact Factor
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Institutions
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1992–2012
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Universidad de Navarra
- • Ciencias cardiovasculares
- • School of Medicine
Pamplona, Navarre, Spain
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2007
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Leids Universitair Medisch Centrum
- Department of Clinical Epidemiology
Leiden, South Holland, Netherlands
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