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F Gianfagna,
C Tamburrelli,
B Vohnout,
M Crescente,
B Izzi,
A Pampuch,
A De Curtis,
A Di Castelnuovo,
A Cutrone,
E Napoleone,
B Tayo,
R Lorenzet,
L Nanni,
M Arca, M B Donati,
G de Gaetano,
C Cerletti,
L Iacoviello
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ABSTRACT: BACKGROUND AND AIMS: Variations in mixed platelet-leukocyte conjugate formation in human whole blood could be genetically determined. We quantified platelet and leukocyte activation and interaction in families with or without early myocardial infarction and evaluated their heritability, genetic correlation and linkage to the 9p21.3 region. METHODS AND RESULTS: The study population included 739 subjects (≥15 years old) from 54 large pedigrees, 23 with and 31 without familial myocardial infarction. Mixed platelet-leukocyte conjugates and markers of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface expression) were measured both before and after in vitro blood stimulation with collagen-ADP. All traits had significant genetic components (17.5-65.3% of the phenotypic variability), while shared household effects (0-39.6%) and environmental covariates (0-10.2%) tended to be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) and platelet-monocyte conjugates showed the highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively; empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically correlated between them in bivariate analysis among pairs of quantitative traits. CONCLUSION: This study supports a genetic regulation of human mixed platelet-leukocyte conjugates.
Nutrition, metabolism, and cardiovascular diseases: NMCD 05/2012; · 3.52 Impact Factor
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ABSTRACT: La limite entre la santé et la maladie est souvent établie par un équilibre complexe entre deux éléments, génétique d’une
part et style de vie de l’autre. Mieux le comprendre signifie mettre de nouvelles armes, souvent essentielles, à la portée
des médecins et de leurs patients. Ceci implique aussi l’adaptation de thérapies afin de trouver le médicament approprié pour
le patient et la meilleure stratégie de prévention qui sera efficace pour lui ou pour elle. La nutrigénomique est une approche
pour individualiser ou personnaliser l’alimentation et la nutrition, et la santé en fin de compte, en ajustant l’alimentation
au génotype individuel. Dans cette revue, nous présentons l’interaction entre certains polymorphismes génétiques et un certain
régime alimentaire, et un accroissement du risque cardiovasculaire ou d’un cancer. Il est certainement clair, à présent, qu’un
grand nombre de composants des aliments bioactifs peut comporter un risque ou présenter une protection aux différents stades
du processus de formation de l’athérosclérose et du cancer. Nous fournissons, dans cette étude, quelques exemples d’interactions
gène/alimentation qui sont pertinents pour le risque cardiovasculaire et pour le cancer, car un terrain commun pourrait exister
entre la genèse de la maladie cardiovasculaire et certains types de cancers (principalement ceux du tractus gastro-intestinal
et ceux dépendant des hormones).
The border between health and disease is often set by a complex equilibrium between two elements genetics on one hand, lifestyle
on the other, To know it better, means to give new weapons, often crucial, in the hands of the doctors and their patients.
It also means to adjust therapies, to find out which drug is good for a patient and which prevention strategy will work better
for him/her. Nutrigenomics is an approach to individualize or personalize food and nutrition, and ultimately health, by tailoring
the food to the individual genotype. In this review, we present the interaction between certain genetic polymorphisms and
diet and increased cardiovascular or cancer risk. It is, indeed, now clear that a large number of bioactive food components
may provide risk or protection at several stages of both atherosclerosis and cancer formation processes. We are giving here
few examples of gene-food interactions relevant for both the risk of cardiovascular disease and cancer, since a common soil
could exist in the genesis of cardiovascular disease and of some types of cancer (mainly gastrointestinal tract and hormonedependent).
Bio Tribune Magazine 04/2012; 30(1):41-46.
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ABSTRACT: A fatty meal may represent a challenge of in vivo acute inflammatory reaction. We evaluated the acute effects of a standardised fatty meal administration on leukocytes and platelets and on their interactions on 61 subjects at different degree of cardiovascular risk, without any clinical event. Before and 2 hours after a fatty meal, blood cells were counted and markers of leukocyte (intracellular myeloperoxidase [MPO] and Mac-1) and platelet (P-selectin and microparticles) activation and mixed platelet-leukocyte conjugates measured by flow-cytometry. After the fatty meal, both white blood cell and platelet count significantly increased, more markedly in subjects with lower cardiovascular risk score. Mac-1 expression too increased (from 32.2 ± 27.2% to 45.6 ± 29.0%, p=0.0016), while MPO decreased (from 83.1 ± 16.3% to 64.5 ± 23.1%, p<0.0001). A trend for increased platelet activation and interaction with leukocytes was also observed. Women were more markedly susceptible to fatty meal challenge, as compared to men, while age did not seem to affect any cell response to fatty meal. Waist-to-hip ratio and body mass index influenced polymorphonuclear cells (PMN) degranulation and platelet count increase, respectively. Cellular responses to the fatty meal, in particular PMN degranulation, were attenuated in subjects at higher degree of cardiovascular risk, who showed a basal mild inflammatory activation status. In conclusion, a fatty meal consumption may represent a model of acute inflammatory response and appears to be modulated by different demographic and cardiovascular risk degree. This model could be applied to study the effect of food-derived antioxidants or nutritional supplements, but its relevance remains to be demonstrated.
Thrombosis and Haemostasis 03/2012; 107(3):530-7. · 5.04 Impact Factor
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Thrombosis and Haemostasis 11/2011; 106(6):1231-3. · 5.04 Impact Factor
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ABSTRACT: Blood coagulation and inflammation play a key role in atherosclerosis and thrombosis. Candidate gene and genome wide association studies have identified potential specific genes that might have a causal role in these pathogenic processes. The analysis of quantitative traits is more powerful as they are closer to direct gene action than disease phenotypes. Thus linkage-based studies on extended families might be useful both to estimate the heritability and to map the genetic loci responsible for the regulation of the trait. Family-based studies may estimate high heritability for thrombosis and quantitative traits regarding both platelet aggregation and blood coagulation. Some specific loci relevant to thrombosis have been identified, with some of them showing a direct pleiotropic effect on the risk of thrombosis. Haemostasis factors can be activated by inflammatory stimuli. Fibrinogen level is genetically correlated with C-reactive protein levels with a link for both traits on chromosomes 12 and 21. Genes related to prostanoid biosynthesis, involved both in inflammation and thrombosis, show high heritability levels in both enzyme expression and prostanoid production. Considering that few large family-based linkage studies have as yet been performed on haemostasis and inflammation-related traits, additional studies are highly needed. We are performing a family-based linkage study on large pedigrees (750 subjects from 23 families with juvenile myocardial infarction and 31 control families), to identify genes responsible for quantitative traits involved in the pathway progressively going from inflammation to haemostasis, cell activation, thrombus formation and cardiovascular events.
Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2011; 21(11):857-61. · 3.52 Impact Factor
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R di Giuseppe,
A Arcari,
M Serafini,
A Di Castelnuovo,
F Zito,
A De Curtis,
S Sieri,
V Krogh,
N Pellegrini,
H J Schünemann, M B Donati,
G de Gaetano,
L Iacoviello
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ABSTRACT: Antioxidant-rich foods may favorably influence lung function. We examined possible associations between the total dietary antioxidant capacity (TAC) and pulmonary function in a healthy Italian population.
Until May 2009, 22,300 persons were randomly recruited from the general population in the Moli-sani project. A sample only including healthy women (5824) and men (5848) was analyzed. TAC was measured in foods by three different assays and the ferric reducing-antioxidant power (FRAP) assay was selected as the better indicator of dietary TAC. The European Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The association between quintiles of dietary FRAP and pulmonary indexes was assessed using analysis of variance separately for men and women.
After adjustment for confounders, women in the highest quintile of FRAP intake had +39 ml forced expiratory volume in the first second (FEV(1)) and +54 ml forced vital capacity, compared with those in the lowest quintile (P for trend ≤0.006). Stratified analysis showed that this relationship only occurred in women who were premenopausal/never smokers. In this subgroup, the observed effect of higher FRAP intake on FEV(1) was equivalent to an improvement in pulmonary age of 3.3 years. In men, all significant associations between pulmonary function and TAC were lost after adjustment for confounding.
Dietary TAC may have a favorable role in respiratory health, particularly in premenopausal/never smoker women.
European journal of clinical nutrition 08/2011; 66(1):61-8. · 3.07 Impact Factor
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ABSTRACT: Genome-Wide Association Studies found some variants on chromosome 9p21 associated with type 2 diabetes (T2D). We performed a meta-analysis to estimate strength, accuracy and feature of the association of polymorphisms in 9p21 with T2D.
Articles were retrieved screening electronic databases and cross references. Twenty-two publications were identified, for a total of 38,455 T2D patients and 60,516 controls. Twenty-one studies investigated the role of the SNP rs10811661; in some studies three additional SNPs (rs564398, rs10757278, rs1333040) were genotyped. Population attributable risk (PAR) was computed as: risk allele frequency∗(OR-1)/OR, using the per-allele odds ratio (OR). The risk allele (T) of rs10811661 was associated with T2D in most of the studies. In meta-analysis the overall per-allele OR was 1.24 (95% CI: 1.21-1.27; P < 10(-15)), with no difference according to ethnicity (P = 0.45), and low heterogeneity (P = 0.040) across studies partly explained by sample size. Modeling of inheritance suggested an additive effect of the T allele. PAR of T2D related to this polymorphism was 15% for Caucasians and 13% for Asians. The overall odds ratio for the T allele of the SNP rs564398 was 1.08 (95% CI: 1.05-1.12; PAR = 6%). The other SNPs showed negligible associations.
This meta-analysis provides accurate and comprehensive estimates of the association of some genetic variants at chromosome 9p21 and T2D. A relatively small but significant role of the T allele of the rs10811661 SNP in increasing by 21-27% the risk of T2D in an additive way was apparent.
Nutrition, metabolism, and cardiovascular diseases: NMCD 02/2011; 22(8):619-25. · 3.52 Impact Factor
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J Arnaud,
M de Lorgeril,
T Akbaraly,
P Salen,
J Arnout,
F P Cappuccio,
M C J M van Dongen, M B Donati,
V Krogh,
A Siani,
L Iacoviello
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ABSTRACT: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population.
Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)).
Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.
Nutrition, metabolism, and cardiovascular diseases: NMCD 12/2010; 22(6):517-24. · 3.52 Impact Factor
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R di Giuseppe,
A Di Castelnuovo,
C Melegari,
F De Lucia,
I Santimone,
A Sciarretta,
P Barisciano,
M Persichillo,
A De Curtis,
F Zito,
V Krogh, M B Donati,
G de Gaetano,
L Iacoviello
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ABSTRACT: BACKGROUND AND AIMS: The overall consumption of foods most frequently consumed in a typical Italian breakfast might be associated with a better cardiovascular risk profile in Italian adults. METHOD SAND RESULTS: 18,177 subjects (53,2% women), aged ≥ 35 yrs, randomly selected from the Moli-sani Project population were studied. The European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ was used for dietary assessment. To derive breakfast pattern, an "a priori" approach was used: firstly, foods typical of the Italian breakfast were selected: milk, coffee, tea, yogurt, crispbread/rusks, breakfast cereals, brioche, biscuits, honey, sugar and jam. The breakfast score was obtained adding the amounts of all selected foods, expressed in grams/day, previously standardized to mean zero and standard deviation 1. Subjects showing a higher breakfast score appeared to be younger, more frequently women or smokers, with higher social status but less likely practicing physical activity. After multivariable analyses, subjects with a higher breakfast food consumption had a lower risk to have high body mass index, abdominal obesity, systolic and diastolic blood pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all) and C Reactive Protein (P = 0.022). The associations were unrelated to age, sex, smoking, obesity, physical activity and social status. Subjects with a higher food breakfast score also showed a better physical healthy status score, a lower risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P < 0.0001 for both women and men). CONCLUSION: Consumption of typical Italian breakfast foods positively affects CVD risk profile in an adult Italian population.
Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2010; 22(4):347-54. · 3.52 Impact Factor
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M. DE GAETANO,
G. QUACQUARUCCIO,
A. PEZZINI,
M. C. LATELLA,
A. DI CASTELNUOVO,
E. DEL ZOTTO,
A. PADOVANI,
C. LICHY,
C. GROND-GINSBACH,
M. GATTONE,
P. GIANNUZZI,
N. NOVAK,
J. DORN,
M. TREVISAN, M. B. DONATI,
L. IACOVIELLO
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ABSTRACT: Summary Objective: The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. Methods: Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. Results: After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24–0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57–1.00) and haplotype-pair H3–H3 (OR = 0.43, 95% CI 0.20–0.92). Conclusions: TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.
Journal of Thrombosis and Haemostasis 07/2009; 7(9):1465 - 1471. · 5.73 Impact Factor
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F Centritto,
L Iacoviello,
R di Giuseppe,
A De Curtis,
S Costanzo,
F Zito,
S Grioni,
S Sieri, M B Donati,
G de Gaetano,
A Di Castelnuovo
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ABSTRACT: Dietary habits have been associated with cardiovascular disease (CVD) risk factors. This study aimed at evaluating the association of non-predefined dietary patterns with CVD risk profile and C-reactive protein (CRP).
We analyzed 7646 healthy subjects from the Moli-sani project, an on-going cross-sectional cohort study of men and women aged >or=35, randomly recruited from a general Italian population. The Italian EPIC food frequency questionnaire was used. Food patterns were generated using principal factor analysis (PFA) and reduced rank regression (RRR). Three dietary patterns were identified by PFA. The "Olive Oil and Vegetables" pattern, characterized by high intake of olive oil, vegetables, legumes, soups, fruits and fish, was associated with relatively lower values of glucose, lipids, CRP, blood pressure and individual global CVD risk score. The "Pasta and Meat" pattern, characterized by high intake of pasta, tomato sauce, red meat, animal fats and alcohol, was positively associated with glucose, lipids, CRP and CVD risk score. The "Eggs and Sweets" pattern, characterized by positive loadings of eggs, processed meat, margarines, butter, sugar and sweets, was associated with high values of CRP. The first RRR pattern was similar to the "Pasta and Meat" pattern both in composition and association with CVD risk profile.
In a large healthy Italian population, non-predefined dietary patterns including foods considered to be rather unhealthy, were associated with higher levels of cardiovascular risk factors, CRP and individual global CVD risk, whereas a "prudent-healthy" pattern was associated with lower levels.
Nutrition, metabolism, and cardiovascular diseases: NMCD 03/2009; 19(10):697-706. · 3.52 Impact Factor
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A Arcari,
F Zito,
A Di Castelnuovo,
A De Curtis,
C Dirckx,
J Arnout,
F P Cappuccio,
M C J M van Dongen,
M De Lorgeril,
V Krogh,
A Siani, M B Donati,
G De Gaetano,
L Iacoviello
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ABSTRACT: Differences in C-reactive protein (CRP) levels and its determinants in three European populations at different risk of coronary artery disease (CAD) were studied.
Subjects were recruited randomly in Limburg (Belgium), Abruzzo (Italy) and south-west (SW) London (England).
Ten-year risk of fatal coronary events (estimated using risk equations provided by the SCORE Project) was lower both in men and women from Abruzzo, intermediate in people from Limburg and higher in subjects from SW London. Within each country, high sensitivity (hs)-CRP levels were higher in the high-risk class in men but not in women. Men from Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women always had higher hs-CRP levels than men. The strongest hs-CRP determinant was body mass index (BMI, R(2) = 0.14) in women and waist circumference (WC, R(2) = 0.046) in men. The highest hs-CRP levels were observed in subjects with both high BMI and high WC. Metabolic syndrome was associated with high levels of CRP both in men and women, even after adjustment for confounders.
Difference in CRP levels cannot explain the European gradient of CVD risk, although CRP levels are associated with the calculated SCORE risk of fatal coronary events within each country.
Journal of Thrombosis and Haemostasis 04/2008; 6(3):436-43. · 5.73 Impact Factor
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ABSTRACT: Obesity is a major modifiable risk factor for cardiovascular disease. Leptin, the hormone synthesized and released primarily by adipose tissue and found increased in obese individuals, has been implicated in the regulation of inflammation and arterial and venous thrombosis.
To investigate the role of tissue factor (TF), the pivotal agonist of the clotting cascade, as a link between obesity and cardiovascular disease.
In 15 obese patients, plasma levels of leptin and TF as well as TF expression in resting and endotoxin-stimulated mononuclear leukocytes (MN) were increased when compared with healthy donors. In a selected sample of obese patients, loss of body weight led to decreased circulating leptin levels, accompanied by a reduction in plasma TF as well as in TF expression, both in resting and endotoxin-stimulated MN. In subsequent in vitro experiments, leptin was incubated with MN from healthy subjects. Leptin induced TF activity and antigen in a dose-dependent fashion, as assessed by clotting assay and ELISA, respectively. Increased migration of c-Rel/p65 into the nucleus, as determined by EMSA, and development of TF mRNA in monocytes, as assessed by RT-PCR, were observed. Experiments with mitogen-activated protein kinase (MAPK) inhibitors, indicated the involvement of p38 and ERK1/2 pathways.
The presence of TF-expressing MN in blood from obese subjects and the in vitro induction of TF by pharmacologic concentrations of leptin in MN from healthy subjects suggest that TF expression by leptin-stimulated monocytes may contribute to the cardiovascular risk associated with obesity.
Journal of Thrombosis and Haemostasis 07/2007; 5(7):1462-8. · 5.73 Impact Factor
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Journal of Thrombosis and Haemostasis 04/2007; 5(3):621-3. · 5.73 Impact Factor
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Journal of Thrombosis and Haemostasis 04/2007; 5(3):458-60. · 5.73 Impact Factor
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ABSTRACT: Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin.
We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 microm). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucyl-phenylalanine-induced PMN TF expression.
In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.
Journal of Thrombosis and Haemostasis 01/2007; 4(12):2593-8. · 5.73 Impact Factor
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ABSTRACT: Increased levels of sP-selectin, a member of the selectin family involved in the transient attachment of leukocytes to endothelial cells, are found in a number of conditions including diabetes and ischemic heart disease. A number of polymorphisms in the gene encoding P-selectin have been identified. The purpose of the present study was to explore the role of three non-synonymous P-selectin gene polymorphisms, Tyr715Pro, Asn562Asp and Ser290Asn, in determining the risk of macrovascular complications in type 2 diabetic patients.
Following a cross-sectional case-control design from 837 Italian type 2 diabetics, 301 cases with at least one episode of angina pectoris (AP), acute myocardial infarction (AMI), stroke, transient ischemic attacks (TIA) or peripheral arterial disease (PAD) were compared with 536 controls free of ischemic vascular complications in the period preceding the examination. Case subjects had longer duration of diabetes at the time of examination and were older as compared with controls. Hypertension and male sex were over-represented among cases. Allele frequency and genotype distribution of the three polymorphic variants did not show any significant preferential association in groups of cases or controls. Odds ratios also indicated no effect on risk of cardiovascular disease even after adjustment for potentially confounding variables. There was a strong allelic association between Tyr715Pro and Asn562Asp (D' = -0.99, P < 0.0001). Ser290Asn was in linkage disequilibrium with Tyr715Pro (D' = 0.43, P = 0.15) and in almost complete equilibrium with Asn562Asp (D' = 0.05, P = 0.5). Haplotype phase inferred from genotypic data revealed the presence of 6 haplotypes. Global test of significance showed no difference in three marker haplotype distribution between cases and controls (P = 0.88, df = 5).
The present study excludes a major contribution of Tyr715Pro, Asn562Asp and Ser290Asn P-selectin polymorphisms to a susceptibility to ischemic vascular complications in type 2 diabetes.
Nutrition, metabolism, and cardiovascular diseases: NMCD 09/2006; 16(6):418-25. · 3.52 Impact Factor
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ABSTRACT: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis.
To study whether polymorphonuclear leukocytes (PMN) are a source of TF.
Human PMN were carefully separated from other blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeuPhe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flow-cytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation only modifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively.
These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMN TF supports the relevance of inflammatory cells and their interaction with platelets for fibrin deposition and thrombus formation.
Journal of Thrombosis and Haemostasis 07/2006; 4(6):1323-30. · 5.73 Impact Factor
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Journal of Thrombosis and Haemostasis 06/2006; 4(5):1156-7; author reply 1157-8. · 5.73 Impact Factor
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ABSTRACT: BACKGROUNd: Plasminogen activator inhibitor (PAI)-1 plays an important role in inflammation and tissue remodeling. Recently, the -675 4G/5G PAI-1 polymorphism has been linked with asthma.
This study was undertaken to evaluate associations of the -675 4G/5G PAI-1 polymorphism with functional and immunologic parameters of newly diagnosed house dust mite-sensitive allergic asthmatics (HDM-AAs).
This study was performed in 127 HDM-AAs, who responded with at least 20% fall of forced expiratory volume during the first second (FEV(1)) to a bronchial challenge with Dermatophagoides pteronyssinus allergen and during the follow up observation fulfilled GINA criteria for mild-moderate asthma. About 89 healthy control nonatopic subjects (HCs) were used as controls.
The frequency of 4G allele was greater in HDM-AAs (0.69; 95% CI: 0.62-0.76) than in HCs (0.55; 95% CI: 0.48-0.62; P = 0.0034). The PAI-1 polymorphism was associated with an increased risk of HDM-AA; adjusted for sex and age odds ratio was 2.62; (95% CI: 1.16-5.92) for 4G/5G genotype and 3.48 (95% CI: 1.54-7.89) for 4G/4G genotype compared with 5G/5G genotype. Total serum immunoglobulin E (tsIgE) level in 4G/4G homozygotes (557 +/- 343 kU/l) was significantly greater than in 5G/5G homozygotes (241 +/- 288 kU/l; P < 0.001). Both nonspecific and allergen-specific bronchial reactivities were greater in 4G/4G homozygotes than in 5G/5G homozygotes. 4G/4G genotype was associated with significantly higher morning plasma PAI-1 concentration in HDM-AAs and HCs. Morning plasma PAI-1 concentration correlated significantly with log(PC20) (r = -0.39; P = 0.0001) and with log(tsIgE) (r = 0.247; P = 0.0117).
These results support the hypothesis linking the 4G/4G PAI-1 genotype with an increased risk of allergic asthma, bronchial hyperreactivity, and increased tsIgE levels.
Allergy 03/2006; 61(2):234-8. · 6.27 Impact Factor
