Evidence of hypercoagulability and inflammation in young patients long after acute cerebral ischaemia

Anžej, Saša; Božič, Mojca; Antovič, Aleksandra; Peternel, Polona; Gašperšič, N.; Rot, Uroš; Tratar, Gregor; Stegnar, Mojca

doi:10.1016/j.thromres.2006.08.005

Cited by 30 publications

(19 citation statements)

References 40 publications

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“…However, human studies and evidence from murine models suggest a significant role of the SELP gene in the pathogenesis of atherosclerosis and CVD. P‐selectin levels are associated with incident myocardial infarction [55,56], carotid plaque burden and stroke [57,58] and disease activity in peripheral arterial disease [59]. Conversely, individuals with the Thr715Pro polymorphism variant, which we found to be associated with lower soluble P‐selection concentrations, have been reported to experience a reduced risk of myocardial infarction [24,60,61].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic correlates of soluble P‐selectin in the community

Lee

Larson

Lunetta

et al. 2008

Journal of Thrombosis and Haemostasis

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genetic correlates of soluble P-selectin in the community. J Thromb Haemost 2008; 6: 20-31.Summary. Background: P-selectin is a cell adhesion molecule that is involved in atherogenesis, and soluble concentrations of this biomarker reflect cardiovascular risk. However, the clinical correlates and genetic characterization of soluble P-selectin have not been clearly elucidated. Objective: To describe clinical and genetic correlates of circulating P-selectin in the community. Methods: In Framingham Heart Study Offspring (European descent) and Omni (ethnic/racial minority) participants, we examined the association of cardiovascular risk factors with soluble P-selectin concentrations. In Offspring participants, we evaluated heritability, linkage and association of 29 SELP single-nucleotide polymorphisms (SNPs) with adjusted Pselectin concentrations. Results: In multivariable analysis of 3690 participants (54% women, mean age 60 ± 10 years), higher log-transformed P-selectin concentrations were inversely associated with female sex and hormone replacement therapy, and positively associated with age, ethnic/racial minority status, cigarette smoking, waist circumference, systolic blood pressure, fasting glucose, and total/high-density lipoprotein cholesterol and triglyceride concentrations. Clinical factors explained 10.4% of the interindividual variability in P-selectin concentrations. In 571 extended pedigrees (n = 1841) with ‡ 2 phenotyped members per family, multivariable-adjusted heritability was 45.4 ± 5.8%. Among the SELP SNPs examined, a nonsynonymous SNP (rs6136) encoding a threonine-to-proline substitution at position 715 was highly significantly associated with decreased P-selectin concentrations (P = 5.2 · 10 )39), explaining 9.7% of variation after adjustment for clinical factors. Conclusions: Multiple clinical factors and an SNP in the SELP gene were significantly associated with circulating Pselectin concentrations. One SNP in SELP explained significant variation in circulating P-selectin concentrations, even after accounting for known clinical correlates.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic correlates of soluble P‐selectin in the community

Lee

Larson

Lunetta

et al. 2008

Journal of Thrombosis and Haemostasis

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“…Particularly IL-1β, IL-6 and IL-8 are present in whole blood, and measurable (in pg.mL −1 ) in most systemic inflammatory conditions. An important hallmark of systemic inflammation is a pathological coagulation potential, and hypercoagulation is also found in (most) inflammatory conditions (discussed extensively in refs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). …”

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confidence: 99%

Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity

Bester

Pretorius

2016

Sci Rep

252

206

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Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot formation, erythrocyte pathology and platelet hyper-activation, and these three cytokines have known receptors on platelets. Although these cytokines are always unregulated in inflammation, we do not know how the individual cytokines act upon the structure of erythrocytes and platelets, and which of the viscoelastic clot parameters are changed. Here we study the effects of IL-1β, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. Erythrocyte structure was notably affected in the presence of IL-8, where the morphological changes resembled that typically seen in eryptosis (programmed cell death). We suggest that erythrocytes and platelets are particularly sensitive to cytokine presence, and that they are excellent health indicators.

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“…The main evidence which supports this assertion lies with the statistically extremely significant extension of euglobulin lysis clot time in the patient group when compared to the control group (p=0.005). Other studies share the same conviction, proposing that patients with an acute cerebral infarction do have a fibrinolytic disorder and suggesting that these abnormalities in the hemostatic mechanism can be considered a risk factor for ischemic brain disease (25,26).…”

Section: Discussionmentioning

confidence: 89%

Decrease of Fibrinolytic Potential in the Occurence of Cerebral Ischemia

Vučković¹,

Đerić²,

Ilić³

et al. 2008

Journal of Medical Biochemistry

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Summary:One of the most present clinical manifestations of long and progressive atherothrombotic occurrences is the ischemic cerebrovascular insult, one of the leading causes of death and illness in the world. Lately, a growing number of scientists believe that disorders in the fibrinolytic mechanism function are the key to the occurrence of cerebral ischemia. The goal of this study is to investigate whether the disorder of the fibrinolytic mechanism has influence on the occurrence of ischemic cerebrovascular insult. Our study includes 90 examinees, 60 of which suffer from ischemic cerebrovascular insult and 30 are clinically healthy examinees forming the control group. The results of our investigation show that statistically a significantly larger number of patients has decreased fibrinolytic potential comparing with controls (p<0.01). According to this, it has been noted that euglobulin lysis clot time in the patient group is significantly longer (p=0.005). Statistically, no significant difference has been noted related to the activity of plasminogen (p=0.085). Further on, the plasminogen activator inhibitor-1 values among the patients have been significantly higher (p=6.20×10 ). The results of this investigation impose the conclusions that the decrease in fibrinolytic potential affects the occurrence of ischemic cerebrovascular insult, that it is directly connected to the higher levels of plasminogen activator inhibitor-1 and that the growth of tissue-type plasminogen activator antigen concentration participates in the decrease of fibrinolytic potential among patients suffering from cerebral ischemia. Keywords: fibrinolytic system, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor-1 Kratak sadr`aj: Jedna od naj~e{}ih klini~kih manifestacija dugotrajnih i progresivnih aterotrombotskih zbivanja je ishemijski cerebrovaskularni insult. To oboljenje se danas nalazi me|u vode}im uzrocima morbiditeta i mortaliteta u ve}ini zemalja. U poslednje vreme sve je ve}i broj nau~nika koji smatraju da su poreme}aji fibrinoliznog mehanizma kljuñ astanka cerebralne ishemije. Cilj na{e studije bio je upravo da ispitamo da li poreme}aj fibrinoliznog mehanizma ima uticaja na nastanak ishemijskog cerebrovaskularnog insulta. U studiju je uklju~eno 90 ispitanika, od toga 60 bolesnika koji su do`iveli cerebrovaskularni insult po tipu ishemije i 30 klini~ki zdravih osoba, koje su ~inile kontrolnu grupu. Rezultati na{eg istra`ivanja ukazuju na statisti~ki zna~ajno ve}i broj ispitanika sa suprimiranim fibrinoliznim potencijalom u grupi bolesnika u odnosu na kontrolnu grupu (p<0,01). U skladu s tim, ustanovljeno je statisti~ki zna~ajno du`e euglobulinsko vreme lize koaguluma me|u bolesnicima nego me|u kontrolama (p=0,005). Nije uo~ena statisti~ki zna~ajna razlika u aktivnosti plazminogena izme|u te dve grupe ispitanika (p=0,085), dok su vrednosti inhibitora aktivatora plazminogena-1 (p=6,20×10 -11 ) i antigena tkivnog aktivatora plazminogena (p=5,20×10 -5 ) statisti~ki zna~ajno vi{e u grupi bolesnika. Ov...

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Evidence of hypercoagulability and inflammation in young patients long after acute cerebral ischaemia

Cited by 30 publications

References 40 publications

Clinical and genetic correlates of soluble P‐selectin in the community

Clinical and genetic correlates of soluble P‐selectin in the community

Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity

Decrease of Fibrinolytic Potential in the Occurence of Cerebral Ischemia

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