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Biomedical subjects

Ginés Escolar

Publications and source records attributed to Ginés Escolar.

At least 19 recordsLinked to original sources
PubMed2006

Effects of etamsylate on equine platelets: in vitro and in vivo studies.

The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study, citrated blood was incubated with different concentrations of etamsylate, and P-selectin expression and annexin V binding were determined by flow cytometry. In the in vivo study, blood was collected before and 1 and 2h after IV administration of etamsylate, and P-selectin expression was evaluated. In the in vitro study, a significant increase in P-selectin expression, leukocyte-platelet aggregate formation and annexin V binding were observed. In the in vivo study, a marked increase in P-selectin expression and heterotypic aggregate formation was seen in two and five horses, respectively, although no significant differences were detected when analyzing results from all the animals together. The results of the in vitro study indicate that etamsylate produces a pre-activation state in equine platelets, but this fact could be confirmed by the in vivo study.

Animals↗
PubMed2006

Serotonergic mechanisms: a potential link between affective disorders and cardiovascular risk.

Cardiovascular disease and major depression are highly prevalent disorders in our society. Evidence has been found that confirms a reciprocal relationship between mechanisms of depression and those of cardiovascular pathology. This possible feedback between both pathologies is a subject of great concern. In recent years some studies suggest that platelets and serotonergic mechanisms could be involved in both conditions. The present review seeks a better understanding of the mechanisms that could link depression with an enhanced cardiovascular risk.

Journal Article↗
PubMed2006

Argatroban: a direct thrombin inhibitor with reliable and predictable anticoagulant actions.

Pharmacological strategies aimed at the prevention of thrombotic complications are in continuous development. Argatroban is a synthetic small molecule derived from l-arginine with specific antithrombotic activity. Argatroban is a direct thrombin inhibitor that binds avidly and reversibly to the catalytic site of thrombin and that does not require other cofactors to exert its antithrombotic action. Due to its selective inhibitory mechanism, argatroban blocks both circulating and clot-bound thrombin. A rapid onset of its anticoagulant action is achieved after intravenous administration. The short elimination half-life of argatroban (52+/-16 minutes) ensures a rapid restoration of hemostasis upon cessation of treatment. Argatroban produces a predictable dose response, and its anticoagulant actions can be monitored easily through the routine coagulation tests activated partial thromboplastin time (aPTT) and activated clotting time (ACT). The specific mechanism of action and favorable pharmacokinetic profile of argatroban suggest that it could be beneficial in all indications where other intravenous anticoagulants are used. Results from clinical studies performed to date show that, when administered to patients with heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITTS) in two large-scale, nonrandomized, prospective trials, argatroban reduced a combined endpoint of morbidity and mortality when compared with historical controls. Argatroban was well tolerated in clinical trials of patients with HIT and caused no increase in bleeding risk compared with historical controls. Argatroban does not induce the formation of antibodies that can neutralize its anticoagulant effect, prolong its half-life or enhance its activity. The U.S. Food and Drug Administration has approved the use of this drug as an alternative antithrombotic treatment for patients with HIT as well as for patients with or at risk for HIT undergoing percutaneous coronary interventions. In 2004 (Sweden), 2005 (Germany, the Netherlands, Austria and Iceland) and 2006 (Denmark) argatroban was approved for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy.

Animals↗
PubMed2005

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites.

Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis.

Ascites↗
PubMed2005

Serotonergic mechanisms: a potential link between affective disorders and cardiovascular risk.

Cardiovascular disease and major depression are highly prevalent disorders in our society. Evidence has been found that confirms a reciprocal relationship between mechanisms of depression and those of cardiovascular pathology. This possible feedback between both pathologies is a subject of great concern. In recent years some studies suggest that platelets and serotonergic mechanisms could be involved in both conditions. The present review seeks a better understanding of the mechanisms that could link depression with an enhanced cardiovascular risk.

Antidepressive Agents↗
PubMed2004

Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.

BACKGROUND: Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5-HT2A) receptor subtype. However, the extrapolation of findings to humans has been inconclusive. A physiological platelet response mediated by this receptor, the serotonin-amplified platelet aggregation, was measured to study whether long-term antidepressant treatment induces changes in 5-HT2A receptor functioning in endogenous depressed patients. METHOD: The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was studied in 15 untreated patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle scale). This index was used as an indirect measurement of the functional status of platelet 5-HT2A receptors. Aggregation studies were repeated once remission of the symptoms was achieved during treatment with imipramine (150-300 mg/day). A group of 15 concurrent normal subjects was used as a control. RESULTS: A statistically significant decrease (p = 0.038) in the percentage of serotonin-amplified platelet aggregation to ADP was observed when remission was achieved (after 145 +/- 27 days). CONCLUSIONS: The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs.

Adult↗
PubMed2004

Platelet membrane fragments enhance the procoagulant effect of recombinant factor VIIa in studies with circulating human blood under conditions of experimental thrombocytopenia.

The mechanism of action of recombinant factor VIIa (rFVIIa), which is being considered as an alternative treatment for the control of bleeding episodes in patients with thrombocytopenia, has not been fully characterized. This study was undertaken to explore the effects of rFVIIa and platelet microvesicles on hemostasis in an experimental model of thrombocytopenia. Damaged arterial segments were exposed to thrombocytopenic blood (shear rate 600 s(-1)) either with or without the addition of rFVIIa and/or platelet microvesicles. The presence of fibrin and platelets on the subendothelium were morphometrically quantified and immunolocalization techniques and electron microscopy were used for a more detailed analysis. Both rFVIIa and platelet microvesicles consistently improved fibrin formation on the damaged vascular subendothelium, and microvesicles were shown to be localized at different levels of the fibrin lattice. Further, under conditions of moderate thrombocytopenia, addition of platelet microvesicles potentiated the procoagulant action of rFVIIa. This effect may be due to the phospholipid surface provided by the platelet microvesicles. These studies support the concept that, under conditions of thrombocytopenia, both rFVIIa and platelet microvesicles enhance fibrin formation at sites of vascular damage.

Arteries↗
PubMed2004

Effects of Helicobacter pylori eradication on platelet activation and disease recurrence in patients with acute coronary syndromes.

BACKGROUND: Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. MATERIALS AND METHODS: Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori-positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. RESULTS: No baseline differences were observed between H. pylori-positive and -negative cases. Among H. pylori-positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35-98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51-4.41)] were independent predictors of recurrence. CONCLUSIONS: Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori-infected patients, however, may have an increased risk of recurrence of coronary events.

Acute Disease↗
PubMed2004

The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury.

The hemostatic agent ethamsylate enhances membrane expression of P-selectin in human platelets, but whether this promotes platelet-leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet-leukocyte aggregates under basal conditions and after whole-blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel. Under basal conditions, ethamsylate was unable to modify whole-blood platelet-leukocyte aggregation, but following whole-blood perfusion through a damaged vessel, ethamsylate produced a modest, but significant increase in platelet-leukocyte aggregates (48+/-21 and 45+/-26% above control levels at ethamsylate 20 and 40 microm respectively). In isolated leukocyte plasma membranes, 14C-ethamsylate specifically bound up to an amount of 660 pmol/mg protein. Moreover, at concentrations > or =1 microm, ethamsylate induced an important (100-200%) and significant increase in the P-selectin glycoprotein ligand 1 (PSGL-1) fluorescence signal in isolated leukocytes and was unable to significantly modify the percentage of CD11b-positive cells. However, no significant changes in aggregate formation were found when ethamsylate was incubated with isolated leukocytes and blood was reconstituted and perfused. In isolated platelet cell membranes, anti-P-selectin antibody and the anti-integrin RGD-containing pentapeptide (GRDGS) were unable to displace 14C-ethamsylate binding. In conclusion, ethamsylate specifically binds to plasma membranes of leukocytes, enhances membrane PSGL-1 expression and promotes leukocyte-platelet aggregation in whole-blood perfused through a damaged vascular segment. These results together with the previously observed enhancement of platelet P-selectin membrane expression [Thromb. Res. (2002)107:329-335] confirms and extends the view that ethamsylate acts on the first step of hemostasis, by improving platelet homo- and heterotypic adhesiveness.

Animals↗
PubMed2004

Effect of holding buffy coats 4 or 18 hours before preparing pooled filtered PLT concentrates in plasma.

BACKGROUND: Filtered PLT concentrates (PCs) were prepared in plasma pooling three (for children) or six buffy coats (BCs; for adults) after holding them a maximum of 4 hours (blood bags collected in the afternoon) or 18 hours (blood bags collected in the morning). STUDY DESIGN AND METHODS: With flow cytometry, PCs prepared after holding BCs 4 or 18 hours were compared. BCs removed from whole-blood donations in quadruple bag packs ("top-top") were held 4 or 18 hours before pooling them with a sterile connecting device. After the BCs were centrifuged, the supernatant was transferred through a BC filter (Autostop, Pall Medical) to a CLX bag. Samples for analysis were collected from the whole-blood bag, BCs, and PCs immediately after preparation and after 1, 3, 5, and 7 days of storage on a flat-bed agitator at 22 +/- 2 degrees C. The main PLT membrane glycoproteins (GPs, IIb-IIIa, IV, and Ibalpha), some of their ligands (fibrinogen, fibronectin, and VWF), activation-dependent antigens (CD62P and CD63), and procoagulant activity markers (annexin V and bound coagulation FV-Va) have been studied. RESULTS: In the 12 PCs (six pools of 3 units each group) studied, a minor increase in activation markers during preparation was observed. During the storage, a significant increase in the expression of GPIIb-IIIa, CD62P, CD63, annexin V, and FVa was measured. After 5 days of storage, only the percentage of PLTs with bound fibrinogen was significantly greater in PCs prepared after holding BCs for 4 hours. CONCLUSION: In PCs prepared after holding BCs 4 or 18 hours before pooling and filtering, only a minor significant difference in the percentage of PLTs with bound fibrinogen was found after 5 days of storage. This difference is probably of little, if any, transfusional significance.

Antibodies, Monoclonal↗
PubMed2004

Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK.

BACKGROUND AND OBJECTIVES: Granulocyte colony-stimulating factor (G-CSF) is specific for the granulocytic cell line, although receptors for this cytokine have been found in other cell types including endothelial cells. These observations prompted us to investigate the potential effect of G-CSF on the endothelium. DESIGN AN METHODS: Endothelial cell monolayers were exposed to G-CSF to evaluate: i) signal transduction mechanisms, ii) expression of adhesion receptors at the cell surface, and iii) leukocyte adhesion on EC monolayers. RESULTS: Exposure of human umbilical vein endothelial cells (EC) in culture to G-CSF resulted in the activation of the signal transduction pathways JAK/STAT (JAK-1, STAT-1 and STAT-3) and RAS/MAPK (MAPK p42/44 and p38 MAPK). We also observed significantly increased expression of the adhesion receptors, E-selectin (ELAM-1), vascular endothelial cell adhesion molecule-1 and intracelleular adhesion molecule-1 at the cell surface in response to G-CSF, increases that were followed by an augmented adhesion of leukocytes on the previously exposed EC monolayers. These effects were blocked by the presence of SB203580, a p38 MAPK inhibitor, by U0126, a MAPK p42/44 inhibitor, and by inhibiting the G-CSF receptor with a specific antibody. INTERPRETATION AND CONCLUSIONS: Our results demonstrate that G-CSF increases the expression of adhesion receptors on EC, promoting leukocyte adhesion. This effect seems to be triggered by the signaling events that follow receptor binding. Results from experiments using specific inhibitors suggest that activation of p38 MAPK is required to promote expression of adhesion receptors in endothelial cells and the recruitment of leukocytes in response to G-CSF.

Cell Adhesion↗
PubMed2003

Glycoproteins expression on platelet membrane in inherited macrothrombocytopenias.

INTRODUCTION: Inherited giant platelet disorders (IGPD) are a heterogeneous group of rare diseases characterized by thrombocytopenia, large platelets and variable bleeding symptoms. Glycoprotein (GP) expression on platelet surface in these conditions is poorly characterized. We have investigated the expression of constitutively expressed platelet membrane GP and the response to TRAP activation in a group of patients with different forms of inherited macrothrombocytopenias. MATERIALS AND METHODS: Two patients diagnosed Epstein syndrome (ES), two with Bernard-Soulier syndrome (BSS) and eight with Mediterranean macrothrombocytopenia (MM) were studied using flow cytometry combined to monoclonal antibodies (MoAbs). Mean platelet volume was also measured. RESULTS: In general, there was an increase in the binding of MoAbs directed against platelet membrane GPs in the patients studied (except, obviously, in BSS patients). The observed increase ranged between 0.9 and 3.36 times the value of the control for GPIbalpha, between 1.36 and 7.2 times for GPIIb-IIIa and 0.94 and 8.07 times for GPIV. However, when the observed value was divided by the measured platelet volume, the estimated density was similar to controls in the case of GPIbalpha but were increased for GPIIb-IIIa and GPIV. TRAP activation provoked significant increments in the number of copies of GPIIb-IIIa complexes present on platelet surface in controls (91%), MM patients (49%), but almost no changes in BSS platelets (6%). CONCLUSION: In the group of macrothrombocytopenia studied, an increase in the expression of platelet membrane GP was observed, although a wide variability exists even in patients with the same disorder.

Adolescent↗
PubMed2003

Physical stability of liposomes bearing hemostatic activity.

The physical stability of six liposome systems designed as platelet substitutes was determined on storage at 4 degrees C over a 3-month period under quiescent conditions. Liposomes used were large unilamellar vesicles. Correlation of the n-average mean diameter, polydispersity, zeta-potential and the presence of aminophospholipid on liposome surface (in those preparations which contain phosphatidylethanolamine (PE) and phosphatidylserine (PS)) led to the conclusion that liposomes that mimicked the composition of platelets were the most stable. When a net charge was present in the vesicles (liposomes with PS), the likelihood of aggregation was extremely low. In the period studied, a proportion of 25% of charged lipid (PS) conferred sufficient electrostatic stabilization to prevent vesicle fusion. An increase in this charge did not modify the stability characteristics. PE-containing liposomes behaved in a particular way: when PE content was 50%, the stability of the preparation was limited to 1 month; whereas if the content was 25%, the zeta-potential rose with time, as did the presence of PE in the liposome surface.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2003

Hemostatic effect of activated recombinant factor VII (rFVIIa) in liver disease: studies in an in vitro model.

BACKGROUND/AIMS: There is clinical evidence for the efficacy of activated recombinant factor VII (rFVIIa) in patients with cirrhosis. The exact mechanism of action of rFVIIa in this clinical condition is unknown. We have explored effects of rFVIIa on hemostasis in cirrhotic patients using an in vitro perfusion technique. METHODS: Blood samples were drawn from control donors or from 11 patients previously diagnosed with cirrhosis (seven Child-Pugh B and four Child-Pugh C) and anticoagulated with low molecular weight heparin. rFVIIa was added to blood samples at therapeutic concentrations (0.5 or 1 microg/ml of plasma) and blood was recirculated through annular chambers containing damaged vascular segments. Presence of platelets and fibrin on the subendothelium were morphometrically quantified. RESULTS: Cirrhotic patients showed a diminished platelet interaction with the subendothelium compared to healthy donors (17.3% (9.28-28.88%) vs. 26.16% (19.96-54.5%), P<0.05). After addition of rFVIIa to cirrhotic samples, no differences in platelet covered surface were observed. However, fibrin formation was significantly improved after the addition of rFVIIa (from 51.81% (3.02-86.68%) to 86.94% (30.03-93.18%) and 89.05% (45.65-93.84%), respectively, P<0.05). CONCLUSIONS: Our data confirm a defective interaction of platelets with the subendothelium in cirrhotic patients. rFVIIa improved local fibrin formation at damaged sites and this mechanism could explain the beneficial action of rFVIIa in cirrhotic patients.

Aged↗
PubMed2003

Molecular, ultrastructural and functional characterization of a Spanish family with Hermansky-Pudlak syndrome: role of insC974 in platelet function and clinical relevance.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, which is genetically heterogeneous. In humans, mutations associated with this syndrome have been identified that affect four genes, most of them located in the HPS-1 gene. We evaluated the clinical, molecular, platelet ultrastructure and platelet function data obtained from one Spanish HPS patient and his relatives. The proband was compound heterozygous for a de novo nonsense mutation (Arg-131Stop), which has not been described previously, and for a common frameshift mutation (insC974). These two mutations were also identified by reverse transcription polymerase chain reaction (RT-PCR) in half the RNA, supporting the premise that they have minor effects on either transcription or RNA stability. The patient had an almost complete absence of platelet-dense granules. Accordingly, his platelets showed a small aggregatory response, reduced CD63 surface expression after platelet activation and minor serotonin uptake. Interestingly, despite the absence of clinical symptoms, two relatives carrying only one HPS-1 mutation (insC974) presented a decreased content of platelet-dense granules and showed significant reductions in platelet aggregation, expression of CD63 after platelet activation and serotonin uptake. Data show that the presence of a single mutation affecting one allele of the HPS-1 gene might have relevance in the organogenesis of platelet-dense granules, affecting platelet function. However, these functional defects were not of a great enough magnitude to have clinical significance and, thus, these subjects were clinically asymptomatic.

Blood Platelets↗
PubMed2003

Increased local procoagulant action: a mechanism contributing to the favorable hemostatic effect of recombinant FVIIa in PLT disorders.

BACKGROUND: Recombinant FVIIa (rFVIIa) has been shown to improve hemostasis in patients with thrombocytopenia and to prevent or control bleeding episodes in patients with inherited deficiencies of major PLT glycoproteins, but the mechanism of action is not well understood. STUDY DESIGN AND METHODS: Effects of rFVIIa on hemostasis were explored with an in vitro perfusion technique. Blood samples, from healthy donors or from patients with congenital defects of PLT glycoprotein IIb-IIIa (GPIIb-IIIa), were anticoagulated with low-molecular-weight heparin. Experimental thrombocytopenia (<6000 PLTs/microL) was induced by a filtration procedure. rFVIIa was added to blood samples at therapeutic concentrations. A severe GPIIb-IIIa impairment was also induced by exposure of normal blood samples to a specific antibody. Perfusion studies were performed through annular chambers containing damaged vascular segments. The presence of fibrin and PLTs on the perfused subendothelium was morphometrically quantified. RESULTS: Under conditions of experimental thrombocytopenia, addition of rFVIIa enhanced fibrin formation in a dose-dependent manner (p < 0.05). Improvements in local fibrin generation and partial restoration of PLT interactions were also observed after incubation of blood from patients with Glanzmann's thrombasthenia with rFVIIa at 5 microg per mL (180 microg/kg). Similar improvements were observed in blood samples incubated with antibodies to GPIIb-IIIa. rFVIIa in whole normal blood also enhanced fibrin formation but PLT deposition was unaffected. Evaluation of prothrombin fragments 1 and 2 in the perfusates confirmed that rFVIIa increased thrombin generation in all cases. CONCLUSION: Our data indicate that rFVIIa promotes a procoagulant activity at sites of vascular damage. This mechanism could explain the beneficial hemostatic effect of rFVIIa in patients with thrombocytopenia or with Glanzmann's thrombasthenia.

Blood Coagulation↗
PubMed2003

Uraemic medium accelerates proliferation but does not induce apoptosis of endothelial cells in culture.

BACKGROUND: Chronic renal failure patients exhibit accelerated atherosclerosis, which is associated with a high incidence of cardiovascular death. We investigated the potential effect of uraemic medium on cell proliferation and apoptosis of endothelial cells in culture (ECs), two key processes in the development of atherosclerosis. Phosphorylation kinetics of the mitogen-activated protein kinase (MAPK) p42/44 and p38 were also evaluated. METHODS: ECs were cultured with growth media supplemented with pooled sera from healthy donors. Semiconfluent ECs were incubated for 24 h with media supplemented with pools of control or uraemic sera. Cell proliferation was assessed through morphometric analysis and by flow cytometry evaluation of cell cycle. To investigate if uraemic medium induces apoptosis in ECs, we used a combination of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay and activation of caspase-3 using flow cytometry. Changes in the phosphorylation levels of MAPK were evaluated in cell lysates by western blotting. RESULTS: Exposure to uraemic media caused an alteration in the morphology of ECs, showing irregular shape and size. The number of ECs at S+G(2)M phase in the cell cycle was found to be increased when exposed to uraemic media for 24 h (28.4+/-2.9 vs 20.2+/-2.6% in control ECs). There was a transient increase in levels of phosphorylation of MAPK in both cells, although these levels were significantly higher in ECs exposed to uraemic media, especially after 5 min. In contrast, no signs of apoptosis were observed in ECs incubated with uraemic medium at the conditions applied. CONCLUSIONS: Under our experimental conditions, uraemic medium accelerates proliferation of ECs, but it does not seem to induce apoptosis. The increased proliferation observed could be related to a higher MAPK activity in these cells. Although the enhanced atherosclerosis cannot be explained on the basis of an apoptotic process, the proliferative status could contribute to intimal proliferation, which is considered to be an earlier step in the development of atherosclerosis.

Apoptosis↗