Bożena Karolko

Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide preparation isolated from the medicinal plant Erigeron canadensis L.

The polyphenolic-polysaccharide preparation from Erigeron canadensis L. was isolated by multi-step process, characterized by chromatographic and spectroscopic methods, and was subjected to anion-exchange chromatography. The whole preparation demonstrated in vivo anticoagulant activity, and the effect was neutralized by protamine sulfate. It had also anti-platelet activity, limited to the cyclooxygenase pathway, induced by arachidonic acid. The plant preparation was fractionated to receive the fraction of the highest anticoagulant activity - 7-9IU/mg of heparin standard, expressed in aPTT. The influences of the plant preparation as well as its the most active fraction on thrombin and factor Xa inactivation by antithrombin, and on thrombin inhibition by heparin cofactor II, were compared. The both tested plant preparations inhibited thrombin as well as factor Xa amidolytic activities in the presence of antithrombin, but much higher concentrations were required to obtain the same effects like for unfractionated heparin. The mechanisms of anticoagulant activity in the case of the plant preparation are based on interactions with heparin cofactor II, to inactivate thrombin. Chromatographic and spectroscopic methods revealed its macromolecular polyanionic non-sulfated polyphenolic-polysaccharide conjugate, with carboxylic groups. The polysaccharide part constituted 32% of the total mass and was homogenous, with molecular mass 38kDa, containing mainly hexuronic acids, and much smaller amounts of glucose, arabinose, galactose, as well as some traces of mannose, xylose and rhamnose. Polyphenolic part, with molecular mass >12.5kDa, was rich in hydroxylic rests as well as in carboxylic groups, free and esterified. The polyphenolic-polysaccharide preparation from E. canadensis may become a new source of anticoagulant compound potentially useful in anticoagulant and anti-platelet therapy.

Androgen receptor polymorphism and platelet reactivity in healthy men

There is established evidence of gender differences in the prevalence and severity of vascular thrombosis and mortality, with men having onset of coronary artery disease earlier in the life thanwomen, andwith first symptoms more often being myocardial infarction [1]. The impact of sex hormones on gender differences in platelet activity (one of the main factors in atherothrombosis) is also being increasingly recognized [2]. One of the “culprit” hormoneswhich could play a role in that setting is testosterone, which seems to have an influence on platelet activity, although the available data are conflicting. Some experimental studies show that in castrated rats given testosterone to physiological levels, enhanced platelet aggregation present after castration [3,4] and atherosclerotic plaque growth are inhibited [5]. Testosterone deprivation can also be harmful in men with prostate cancer treated with anti-androgenic therapy [6]. By contrast, in another study, exogenously administered testosterone up-regulated the population of thromboxane A2 (TXA2) receptors onplatelets in healthy youngmale volunteers, and this was concomitant with an enhanced aggregation response to TXA2mimetic I-BOP [7]. In yet another study, the reduction in circulating testosterone concentration following castration was associated with a significant reduction in platelet TXA2 receptor density and maximum aggregation response to TXA2-mimetic I-BOP[8]. Available data therefore suggest that testosterone influences platelet aggregation through increasing or decreasing TXA2 receptor density on the platelet surface. The mechanism for this action is largely obscure. A recent study has suggested the presence of androgen receptors (ARs) within platelets. In this study ADP-induced platelet aggregation was associated with platelet cytosolic binding to radiolabeled testosterone [9]. What is more, humanmegakaryocytes generated ex vivo expressed RNA for AR, confirmed by Western immunoblotting to be present in humanplatelets in another study [10]. These in vitro effects of testosteroneonplatelet aggregation suggestnon-genomic actionsonplatelets, or the presence of functional AR within platelets, which modulate the response to TXA2-induced platelet aggregation [10]. One possible pathway could involve testosterone linking to ARs in platelet cytosol, which in turn up-load TXA2 receptors onto the platelet surface, enhancing aggregation induced by I-BOP (TXA2-receptor agonist). The strength of the testosterone action in vivo is dependent on testosterone level and AR density and structure. ARs are expressed in vascular endothelium, in smooth muscle cells, and presumably within platelets.Genetically, theyareencodedonchromosomeX(locusq11–12). The polyglutaminic sequence coding region is the mostly polymorphic one in that gene and accounts for the transcript activity of the final product. It consists of a periodically repeating nucleotide triplet, the socalled CAG (cytosine, adenine, guanine) repeats [11]. Genetic variations of the AR gene – principally fewer CAG repeats in the amino-terminal domain – has been associated with higher testosterone levels in women

Plasma level of YKL-40 correlates with the severity of coronary atherosclerosis assessed with SYNTAX score

Introduction YKL‑40 is a protein released locally by inflammatory cells. Thus, it may constitute a biomarker of inflammatory conditions, such as atherosclerosis. Objectives The aim of the study was to determine YKL‑40 levels in patients with ischemic heart disease and to analyze the correlation of this biomarker with the severity of coronary atherosclerosis. Patients and methods The study included 158 patients: 52 with stable ischemic heart disease and 67 with acute coronary syndrome: ST‑segment elevation myocardial infarction (STEMI; n = 47) or non-ST‑segment elevation myocardial infarction (NSTEMI; n = 20). The control group included 39 individuals without abnormalities in coronary vessels. We evaluated plasma YKL‑40 levels and their correlation with the severity of coronary atherosclerosis assessed with the SYNTAX score. Results Patients with myocardial infarction had higher plasma YKL‑40 levels than those with stable ischemic disease (median [range], 235.3 [161.6-366.1] ng/ml vs 61.2 [53.1-83.1] ng/ml; P <0.001) or controls (median [range], 235.3 [161.6-366.1] ng/ml vs 55.7 [51.2-75.2] ng/ml; P <0.001). No differences were found in YKL‑40 concentrations between STEMI and NSTEMI patients (median [range], 263 [150.3-363.7] ng/ml and 214.9 [163.4-367.6] ng/ml, respectively; P = 0.7). The SYNTAX score in patients with ischemic heart disease correlated positively with YKL‑40 concentrations (R = 0.34; P <0.001). Conclusions YKL‑40 can be considered a potential biomarker of coronary atherosclerosis severity.

Znaczenie białka ST2 w schorzeniach układu krążenia

Bialko ST2 bierze udzial w odpowiedzi immunologicznej i jest wydzielane w reakcji na mechaniczne rozciąganie miokardium. Jego blonowa izoforma (ST2L) stanowi receptor dla interleukiny 33, ktorej dzialanie zapobiega niekorzystnej przebudowie mieśnia sercowego poprzez antagonizowanie dzialania angiotensyny II i amin katecholowych. sST2 stanowi rozpuszczalną forme bialka, ktore funkcjonując jako receptor wabikowy, uniemozliwia wiązanie sie IL-33 z cząsteczką ST2L i hamuje kardioprotekcyjne szlaki biochemiczne inicjowane przez IL-33. Zaburzenia rownowagi pomiedzy dzialaniem IL-33/ST2 a antagonizującym wplywem sST2 mogą sprzyjac rozwojowi miazdzycy i choroby wiencowej oraz zmniejszac stabilnośc blaszki miazdzycowej, prowadząc do ostrych zespolow wiencowych. Coraz wiecej danych z prowadzonych badan sugeruje, ze sST2 odgrywa istotną role w czynnościowym i strukturalnym remodelingu lewej komory i jej wloknieniu orazmoze dostarczac cennych informacji diagnostycznych i prognostycznych w chorobach ukladu sercowo-naczyniowego. Dynamika seryjnych oznaczen ST2 wskazuje na potencjalną przydatnośc tego biomarkera w monitorowaniu pacjentow z niewydolnością serca oraz w ocenie rokowania u chorych po zawale. W pracy przedstawiono aktualny stan wiedzy na temat udzialu ST2 w patogenezie schorzen ukladu krązenia ze szczegolnym uwzglednieniem jego roli w niewydolności serca oraz mozliwości diagnostycznych i predykcyjnych sST2 jako nowego biomarkera.

Cardiac arrest during percutaneous coronary intervention in a patient 'resistant' to clopidogrel - successful 50-minute mechanical chest compression.

We report a case of 72-year-old female patient with end-stage chronic kidney disease, undergoing percutaneous coronary intervention (PCI) that resulted in a cardiac arrest caused by a thrombus mediated flow limitation in the left coronary artery. With mechanical cardiopulmonary resuscitation (CPR) PCI of the left main artery was performed successfully during 50 min cardiac arrest. The patient was discharged from the hospital without compromising cardiac function and neurological deficits.