Protease-activated receptor-1 expression is not responsible for high reactivity of platelets and leukocytes in ischemic stroke survivors

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA255

Poster Communications: Protease-activated receptor-1 expression is not responsible for high reactivity of platelets and leukocytes in ischemic stroke survivors

O. Sulaieva1, I. Prylutska1, A. Kalmykova2, A. Prylutsky4, V. Dosenko3

1. Histology, Zaporozhye State Medical University, Zaporozhye, Ukraine. 2. Pathology, Zaporozhye State Medical University, Zaporozhye, Ukraine. 3. Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv, Ukraine. 4. Laboratory diagnostics, Neurology, Donetsk National Medical University, Donetsk, Ukraine.

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Ischemic stroke is associated with abnormal platelet and leukocyte reactivity [1]. This determines the induction of pro-inflammatory cascade and further brain injury [2]. As it was shown previously cerebral injury progression and complications development depends on expression of one of the thrombin receptors – protease-activated receptor-1 (PAR1), encoded by F2R [3]. The aim of this study was to estimate whether PAR-1 is involved in platelets and leukocytes abnormal reactivity among patients with ischemic stroke. Methods. Platelets and leukocytes were assessed among 10 patients (males, 54±2,3 years old) with ischemic stroke confirmed by cranial computer tomography. The National Institutes of Health Stroke Scale (NIHSS) scores obtained within 24 hours of acute ischemic stroke symptom onset from patients enrolled in this study was 6-10. In addition to blood cells count, we assessed platelets aggregation induced by thrombin (1,5 NIH) and platelet-leukocyte aggregates (PLA) number in peripheral blood at the time of hospital admission, and after 3, 7 and 14 days after treatment. The PAR-1 mRNA expression was detected by RT-PCR method in isolated platelets and leukocytes. 10 healthy volunteers were taken as a control group. Results. Ischemic stroke was associated with leukocytosis due to increase of segmented neutrophils percentage rates (p=0,026) and PLA formation in peripheral blood. Their number was significantly higher at the moment of hospital admission (p<0,001) and significantly decreased after 7 days after treatment (p<0,001). Thrombin induced prominent platelet aggregation and PLA formation (p<0,01). However, assessment of PAR-1 expression showed alternative results. Expression of PAR-1 in leukocytes was not detectable both among stroke and control groups. In addition in platelets the PAR-1 expression was low in the most of observed patients (p<0,001). Recovery of patients was accompanied with increase of the level of PAR-1 mRNA expression by 14 day (p<0,05), however it didn’t reach the control values (p<0,05). Conclusion. High reactivity of platelets to thrombin and increased PLA formation among patients with ischemic stroke were associated with low PAR-1 expression. It could be related with changes either in PAR-4 expression or in signalling cascades, involved in proinflammatory activation of platelets.



Where applicable, experiments conform with Society ethical requirements.

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