[Show abstract][Hide abstract] ABSTRACT: The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control.
The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity.
In an anaesthetized pig model, a controlled transient coronary occlusion was used to stimulate coronary tissue plasminogen activator release in a valproic acid treated (one week) and a non-treated group. Coronary venous blood samples from the ischemic region were collected, great cardiac vein thermodilution flow measurements were performed, and trans-coronary tissue plasminogen activator fluxes were calculated. Plasminogen activator inhibitor-1 was also measured.
Adequate sampling from the affected area after the 10 minute ischemic period was confirmed by lactate measurements. Fluxes for tissue plasminogen activator at minutes 1, 3, 5, 7 and 10 were measured and then used to present cumulative net tissue plasminogen activator release for the whole measurement period for both groups. Area under the curve was higher for the valproic acid treated group at 10 minutes; 932±173 nanograms (n = 12) compared to the non-treated group, 451±78 nanograms (n = 10, p = 0.023). There was no difference in levels of plasminogen activator inhibitor-1 between groups.
These findings support a proof of concept for histone deacetylation inhibition positive effect on tissue plasminogen activator expression in an in vivo setting. Further studies are needed to find an optimal way to implement histone deacetylation inhibition to achieve desired clinical changes in tissue plasminogen activator expression.
PLoS ONE 01/2014; 9(5):e97260. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigenetically regulated mainly by histone deacetylase (HDAC) inhibitors. HDAC inhibitors, including VPA markedly upregulate t-PA gene expression in vitro.
PLoS ONE 01/2014; 9(10):e107582. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A reduced capacity for acute tissue-type plasminogen activator (t-PA) release is likely to be associated with an impaired endogenous defense against intravascular thrombosis. Efficient approaches to pharmacologically restore a defective t-PA release have been lacking, but recent observations suggest that histone deacetylase inhibitors (HDACis) enhance t-PA production in vitro. HDACis have diverse chemical structures and different HDAC-enzyme sub-class targeting. We here compared the effects of several clinically used HDACis on t-PA production in endothelial cells. Human umbilical vein endothelial cells were exposed to a panel of 11 different HDACis and t-PA mRNA and protein levels were quantified. All HDACis dose-dependently stimulated t-PA mRNA and protein expression with similar maximal efficacy but with different potencies. Already at low concentrations, the majority of inhibitors caused significant and sustained effects on t-PA production. In addition, selected HDACis were capable of normalizing t-PA production when suppressed by the inflammatory cytokine TNF-α. We conclude that HDACis targeting classical HDAC enzymes are powerful inducers of t-PA expression in cultured endothelial cells and could be promising candidates for pharmacological modulation of endogenous fibrinolysis in man.
Journal of Thrombosis and Thrombolysis 11/2012; · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atherosclerotic plaque formation and progression are dependent on local shear stress patterns and inflammatory cytokines. Statins effectively reduce the progression of atherosclerosis and the incidence of cardiovascular events. However, the benefit of statins cannot be explained by cholesterol reduction alone. This study, investigated the non-lipid lowering effects of simvastatin and rosuvastatin on endothelial anti- and prothrombotic genes under different biomechanical and inflammatory stress conditions. Endothelial cells responded in a similar way to simvastatin and rosuvastatin. However, they were more sensitive to simvastatin. The statins had anti-inflammatory properties counteracting the TNF-α effect on the hemostatic genes studied. There was no observed synergistic effect between shear stress and simvastatin. Simvastatin had a counteracting effect on t-PA and PAI-1 compared to TNF-α and shear stress. Simvastatin blocked the TNF-α suppressive effect on thrombomodulin and eNOS, irrespective of shear stress. The strong inductive effect of TNF-α on VCAM-1 was counteracted by simvastatin and shear stress in an additive dose-response dependent way.
Biochemical and Biophysical Research Communications 03/2012; 420(1):166-71. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stimulated release of tissue-type plasminogen activator (t-PA) is pivotal for an intravascular fibrinolytic response and protects the circulation from occluding thrombosis. Hence, an impaired t-PA production is associated with increased risk for atherothrombotic events. A pharmacological means to stimulate the production of this enzyme may thus be desirable. We investigated if the anti-epileptic drug valproic acid (VPA) is capable of enhancing t-PA expression in vitro in vascular endothelial cells, and further examined if its histone deacetylase (HDAC)-inhibitory activity is of importance for regulating t-PA expression.
Human endothelial cells were exposed to valproic acid and t-PA mRNA and protein levels were quantified. Potential changes in histone acetylation status globally and at the t-PA promoter were examined by western blot and chromatin immunoprecipitation. Valproic acid dose-dependently stimulated t-PA mRNA and protein expression in endothelial cells reaching a 2-4-fold increase at clinically relevant concentrations and 10-fold increase at maximal concentrations. Transcription profiling analysis revealed that t-PA is selectively targeted by this agent. Augmented histone acetylation was detected at the t-PA transcription start site, and an attenuated VPA-response was observed with siRNA knock of HDAC3, HDAC5 and HDAC7.
Valproic acid induces t-PA expression in cultured endothelial cells, and this is associated with increased histone acetylation at the t-PA promoter. Given the apparent potency of valproic acid in stimulating t-PA expression in vitro this substance may be a candidate for pharmacological modulation of endogenous fibrinolysis in man.
PLoS ONE 01/2012; 7(2):e31573. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The endogenous fibrinolytic system and the ability of the endothelium to release tissue-plasminogen activator (t-PA) play a pivotal role to protect humans from atherothrombotic events. We have recently reported that the decreased capacity for t-PA release in hypertension is restored with chronic blood pressure lowering. Thus, we explored if acute blood pressure lowering has the same effect. The capacity for acute t-PA release was investigated in the perfused-forearm model during stimulation by intra-arterial substance P 8 pmol/min in hypertensive subjects. The procedure was then repeated during acute blood pressure lowering (n = 9) induced by sodium nitroprusside (SNP) infusion or during placebo infusion (n = 3). SNP lowered mean arterial pressure from 108.6 (2.6) to 83.0 (2.6) (mean and SEM) mmHg (P < 0.001). Substance P induced significant increase in t-PA release during both high- and low-pressure conditions (P < 0.01, ANOVA). Peak t-PA release rate was 199 (77) and 167 (41) (mean and SEM) ng/min/l tissue, and accumulated t-PA release was 2,395 (750) and 2,394 (473) ng, during high- and low-pressure conditions, respectively. t-PA release and hemodynamic responses were almost identical during high- and low-pressure conditions (P = ns, for all). Acute blood pressure lowering does not restore stimulated t-PA release from the endothelium in hypertensive subjects. These findings are in contrast to previously described effects of chronic blood pressure treatment. Although data need to be confirmed in a larger study, they suggest that high blood pressure decreases the cellular t-PA pool rather than interferes with release mechanisms of the protein.
Journal of Thrombosis and Thrombolysis 05/2011; 32(4):399-404. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The vascular fibrinolytic system is crucial for spontaneous lysis of blood clots. Plasminogen activator inhibitor 1 (PAI-1), the principal inhibitor of the key fibrinolytic enzyme tissue-type plasminogen activator (tPA), is present in platelets at high concentrations. However, the majority of PAI-1 stored in platelets has been considered to be inactive. Our recent finding (Brogren H, et al. Blood 2004) that PAI-1 de novo synthesized in platelets remained active for over 24 h, suggested that PAI-1 stored in the α-granules might be active to a larger extent than previously reported. To re-evaluate this issue, we performed experiments where the fraction of active PAI-1 was estimated by analyzing the tPA-PAI-1 complex formation. In these experiments platelets were lysed with Triton X-100 in the presence of serial dilutions of tPA and subsequently the tPA-PAI-1 complex was evaluated by Western blot. Also, using a non-immunologic assay, tPA was labeled with (125)I, and (125)I-tPA and (125)I-tPA-PAI-1 was quantified by scintigraphy. Interestingly, both methods demonstrated that the majority (>50%) of platelet PAI-1 is active. Further analyses suggested that pre-analytical procedures used in previous studies (sonication or freezing/thawing) may have substantially reduced the activity of platelet PAI-1, which has lead to an underestimation of the proportion of active PAI-1. Our in vitro results are more compatible with the role of PAI-1 in clot stabilization as demonstrated in physiological and pathophysiological studies.
PLoS ONE 01/2011; 6(11):e26762. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutic hypothermia has been found to improve hemodynamic and metabolic parameters in cardiogenic shock. Tissue plasminogen activator (t-PA) is a pro-thrombolytic enzyme, which also possesses pro-inflammatory properties. Interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) are pro-inflammatory cytokines; interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-β1) are anti-inflammatory cytokines. The aim of this experiment was to investigate the mechanism behind the protective effect of therapeutic hypothermia in cardiogenic shock. This was done by studying the effect of hypothermia on basal t-PA levels, peripheral t-PA release, and on the inflammatory response. Cardiogenic shock was induced by inflation of an angioplasty balloon in the proximal left anterior descending artery for 40 min in 16 pigs, followed by 110 min of reperfusion. The animals were randomized to hypothermia (33°C, n = 8), or normothermia (n = 8) at reperfusion. Hemodynamic parameters were continuously monitored. Plasma was sampled every 30 min for analysis of blood-gases and t-PA, and for analysis of inflammatory markers at baseline and at the end of the experiment. t-PA, IL-6 and TGF-β1 increased during cardiogenic shock. Apart from favourably affecting hemodynamic and metabolic variables, hypothermia was found to reduce basal arterial and venous t-PA levels, and to inhibit the release of t-PA from the peripheral vascular bed. Hypothermia did not alter the inflammatory response. In conclusion, mild hypothermia improves hemodynamic and metabolic parameters in cardiogenic shock. This is associated with a reduction in basal t-PA levels and t-PA release from the peripheral vascular bed, but not with an altered inflammatory response.
Journal of Thrombosis and Thrombolysis 12/2010; 32(1):72-81. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transcutaneous electrical nerve stimulation (TENS) is an effective treatment option to relieve ischemic pain in refractory angina pectoris (RAP). In healthy persons, TENS enhances local blood flow, but the mechanism responsible for the anti-ischemic effect in RAP seems to be different.
The aim of the present investigation was to compare the difference in blood flow and vasodilatory response to TENS between angina patients and healthy controls and evaluate how vascular response in these groups is affected by amperage dosage above and below motor threshold levels.
Our study evaluated upper limb vascular responses to low- and high-dose TENS (below and above motor threshold) in RAP patients compared with healthy controls. TENS was applied on the nondominating forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Forearm vascular resistance (FVR) was determined (mean arterial pressure [MAP]/FBF). Measurements were done during baseline, low-dose TENS, high-dose TENS, and during recovery.
A significant dose-dependent increase in FBF in response to TENS stimulation was seen in controls (n=18) but not in RAP (n=23) (P=0.008). There was no significant difference in FVR ratio (FVR(stim)/FVR(ctrl)) between control (n=7) and RAP (n=23) groups at low dose (controls, 5.7+/-21%; RAP, 9.7+/-20%) or recovery (controls, -4.6+19%; RAP, 5.9+25%). High-dose TENS resulted in a significantly reduced FVR ratio (-16.8+/-11%) in controls (n=7) compared with RAP (1.6+/-32%, n=23) (P=0.02).
High-dose TENS induces forearm vasodilation in healthy subjects but not in patients with RAP. These findings suggest that TENS has different vascular effects in patients with severe coronary artery disease compared with healthy controls.
Journal of pain and symptom management 07/2010; 40(1):95-101. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify, in a prospective study, how blood pressure levels at the age of twenty predict hypertension and cardiovascular remodelling 20 years later.
Twenty-year-old men with blood pressure (BP) elevation [systolic blood pressure (SBP) 140-160 and/or diastolic blood pressure (DBP) 85-95 mmHg; blood pressure elevation (BPE) group] or normal BP [SBP 110-130 and DBP 60-80 mmHg; normal controls (NC) group] entered the study in 1987. In 2007, follow-up was conducted including ambulatory BP, echocardiography, anthropometric and intima media thickness (IMT) measurements.
Assessed with 24-h ambulatory BP, the prevalence of hypertension was 35/47 (74.5%) and 1/17 (5.9%) in the BPE and NC group at follow-up respectively. Twenty-four hour mean arterial pressure (MAP) increased from 86.6 (0.8) to 97.2 (1.2) (P < 0.0001), and from 83.1 (1.5) to 88.1 (1.2) mmHg (P < 0.01) from baseline to follow-up in the BPE and NC group respectively. At follow-up, left ventricular mass index (LVMI) was 122 (4) and 106 (4) g m(-1) in the BPE and NC group (unpaired t-test; P < 0.01) respectively, whilst IMT was 0.61 (0.01) and 0.57 (0.01) mm in the BPE and NC group (P < 0.05) respectively. In a logistic regression model, prevalence of hypertension was best explained by office MAP and 24-h DBP at baseline (R(2) 0.333; P < 0.05). A combined model of office MAP, body mass index and insulin levels at baseline explained 56% of LVMI at follow-up.
BP elevation in young age predicts hypertension and adverse cardiovascular remodelling at the age of 40 years. Baseline office MAP is the best predictor of hypertension, 24-h MAP and LVMI.
Journal of Internal Medicine 08/2009; 267(3):295-304. · 6.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In experimentally induced myocardial ischemia, mild hypothermia (33-35 degrees C) has a robust cardioprotective effect. Tissue plasminogen activator (t-PA) is a profibrinolytic enzyme that is released from the vascular endothelial cells in response to ischemia and other injurious stimuli. t-PA has also been found to have proinflammatory properties that could contribute to reperfusion injury. We postulated that hypothermia could attenuate t-PA release in the setting of myocardial ischemia. Sixteen 25-30 kg pigs were anesthetized and a temperature of 37 degrees C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34 degrees C) or control (37 degrees C). A doppler flow wire was placed distal to a percutaneous coronary intervention balloon positioned immediately distal to the first diagonal branch of the left anterior descending artery (LAD). The LAD was then occluded for 10 min in all pigs. Coronary blood flow and t-PA was measured before, during and after ischemia/reperfusion. t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus. Net t-PA release over the coronary bed was calculated by subtraction of arterial values from coronary sinus values. An estimate of differences in total t-PA release was calculated by multiplying net t-PA release with the relative increase in flow compared to baseline, measured in relative units consisting of ((ng/ml - ng/ml) x (cm/s/cm/s)). There was no observed difference in t-PA levels in peripheral arterial samples. As shown previously, net t-PA release increased during reperfusion. Hypothermia significantly inhibited the increase in t-PA release during reperfusion (peak value 9.44 +/- 4.34 ng/ml vs. 0.79 +/- 0.45 ng/ml, P = 0.02). The effect was even more prominent when an estimation of total t-PA release was performed with mean peak value in the control group 26-fold higher than in the hypothermia group (69.74 +/- 33.86 units vs. 2.62 +/- 1.10 units, P = 0.01). Mild hypothermia markedly reduces ischemia related coronary tissue plasminogen activator release. The reduction of t-PA release may contribute to the cardioprotective effect of hypothermia.
Journal of Thrombosis and Thrombolysis 07/2009; 29(3):289-95. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Biomechanical stress modulates vascular tone, vascular remodelling and the spatial localisation of atherosclerotic plaques. Inflammatory cytokines, such as TNF-alpha, regulate expression of genes that impair the function of endothelial cells. This study investigates the combinatory effect of different biomechanical stresses and TNF-alpha on the expression of endothelial anti- and prothrombotic genes. Human umbilical vein endothelial cells were exposed to TNF-alpha and different levels of static/pulsatile tensile stress or shear stress. The response in endothelial cells to TNF-alpha was not modulated by tensile stress. However, shear stress was a more potent stimulus. Shear stress counteracted the cytokine-induced expression of VCAM-1, and the cytokine-suppressed expression of thrombomodulin and eNOS. Shear stress and TNF-alpha additively induced PAI-1, whereas shear stress blocked the cytokine effect on t-PA and u-PA. A flow profile characterized by high laminar shear stress seems to render the endothelial cell more resistant to inflammatory stress.
Biochemical and Biophysical Research Communications 06/2009; 385(3):314-8. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low (< or =1.5 dyn/cm(2)) or high (25 dyn/cm(2)) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.
Biochemical and Biophysical Research Communications 01/2009; 379(2):532-6. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD.
Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group.
This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.
[Show abstract][Hide abstract] ABSTRACT: Whether left bundle branch block is associated with cardiovascular events in hypertension with electrocardiographic left ventricular hypertrophy is unknown.
Hypertensive patients with electrocardiographic-left ventricular hypertrophy were randomized to losartan-based or atenolol-based treatment and followed for 4.8 years in the losartan intervention for endpoint reduction in hypertension study. Cox regression models controlling for significant covariates assessed the association of left bundle branch block with cardiovascular events.
At baseline, 564 patients had left bundle branch block and 8567 patients did not. Left bundle branch block was associated with higher heart rate, electrocardiographic-left ventricular hypertrophy, and prior cardiovascular disease (all P < 0.005). In univariate Cox regression analysis, left bundle branch block was not associated with the composite endpoint, stroke, or myocardial infarction (all P > 0.05), and was associated with cardiovascular (8.3 versus 4.5%, P < 0.001) and all-cause mortality (12.1 versus 8.6%, P < 0.005). After adjusting for significant covariates Cox regression analyses showed that left bundle branch block was independently associated with 1.6-fold more cardiovascular death (95% confidence interval 1.12-2.27, P < 0.05), 1.7 fold more hospitalization for heart failure (95% confidence interval 1.15-2.56, P < 0.01), 3.5 fold more cardiovascular death within 1 h (95% confidence interval 1.89-6.63, P < 0.001), and 3.4 fold more cardiovascular death within 24 h (95% confidence interval 1.83-6.35, P < 0.001).
In hypertension with electrocardiographic-left ventricular hypertrophy, left bundle branch block identifies patients at increased risk of cardiovascular mortality, sudden cardiovascular death, and heart failure.
Journal of Hypertension 07/2008; 26(6):1244-9. · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The increased risk of thrombus formation in inflammatory conditions is generally considered to be due to the pro-coagulant effect of inflammatory cytokines. However, cytokines may also decrease the expression of the key fibrinolytic enzyme tissue-type plasminogen activator (t-PA) causing a reduced clearance of emerging intravascular thrombi. This study investigated the effects of the inflammatory cytokines interleukin (IL)-1beta and IL-6 on t-PA gene and protein expression, and elucidated by which signaling mechanisms the effects are mediated.
Cultured human umbilical vein endothelial cells (HUVEC) were exposed to recombinant IL-1beta or IL-6. t-PA mRNA was quantified by real-time RT-PCR and t-PA antigen by ELISA. To clarify signaling mechanisms, selective inhibitors of major cytokine-activated signaling pathways were used. Interactions of nuclear proteins with potential t-PA gene regulatory elements were studied by gel shift assays.
Already at low concentrations, IL-1beta caused a distinct suppression of t-PA transcript and protein levels, mediated primarily by NF-kappaB signaling. This cytokine also increased binding of NF-kappaB subunits to a t-PA specific kappaB element. IL-6 stimulation per se did not affect t-PA mRNA or protein levels whereas soluble IL-6 receptor, in the presence of endogenous IL-6, suppressed t-PA expression.
We conclude that the proinflammatory cytokine IL-1beta impairs fibrinolytic capacity in vascular endothelial cells by an NF-kappaB dependent suppression of t-PA expression. In contrast, an effect of IL-6 on t-PA expression could not be detected, probably due to lack of IL-6 receptor expression on HUVEC.
Thrombosis Research 06/2008; 123(2):342-51. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main inhibitor of intravascular fibrinolysis is plasminogen activator inhibitor 1 (PAI-1) which binds to and irreversibly inhibits tissue plasminogen activator (tPA). PAI-1 is present in blood, both in platelets and in plasma, and PAI-1 levels are associated with risk of atherothrombosis. Several tissues express PAI-1 but the source of plasma PAI-1 is not known. We recently found that platelets can de novo synthesize PAI-1 and the amount synthesized in vitro in 24 hours is 35-fold higher than required to maintain normal plasma levels. Recombinant human PAI-1 expressed in different cell types or secreted naturally by human cell lines, exhibit heterogeneous glycosylation patterns. The aim of this study was to investigate the hypothesis that platelets might be the source of plasma PAI-1 and that the cellular source of PAI-1 can be determined by its tissue-specific glycosylation pattern. PAI-1 was isolated from platelets, macrophages, endothelial cells, adipose tissue, as well as plasma from lean and obese subjects. The glycosylation was analyzed by nanoLC-MS/MS. PAI-1 isolated from cell lysates and conditioned media from macrophages, endothelial cells, and adipose tissue expressed heterogeneous glycosylation patterns. By contrast, no glycans were detected on PAI-1 isolated from plasma or platelets from healthy lean individuals. Hence, our data suggest that platelets may be the main source of plasma PAI-1 in lean individuals. Interestingly, plasma PAI-1 from obese subjects had a glycan composition similar to that of adipose tissue suggesting that obese subjects with elevated PAI-1 levels may have a major contribution from other tissues.
Thrombosis Research 02/2008; 122(2):271-81. · 3.13 Impact Factor