Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function

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Svensson Holm, Ann-Charlotte (författare): Linköpings universitet,Avdelningen för cellbiologi,Avdelningen för läkemedelsforskning,Hälsouniversitetet

Grenegård, Magnus, 1963- (författare): Linköpings universitet,Örebro universitet,Institutionen för läkarutbildning,Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Pathology and Clinical Genetics, County Council of Östergötland, Linköping, Sweden,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Örebro University, Sweden

Ollinger, Karin (författare): Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik

Lindström, Eva (författare): Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet

(creator_code:org_t)

2013-03-27
2014
Engelska.
Ingår i: Platelets. - London, United Kingdom : Informa Healthcare. - 0953-7104 .- 1369-1635. ; 25:2, s. 111-117

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Abstract Ämnesord

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The aim of the present study was to investigate the role of 12-lipoxygenase (12-LOX) on platelet-induced airway smooth muscle cell (ASMC) proliferation. Co-incubation of platelets and ASMC caused platelet activation as determined by morphological changes. Simultaneously, reactive oxygen species (ROS)-generation was detected and ASMC proliferation (measured by using the MTS assay) increased significantly. Furthermore, we found that the 12-LOX inhibitors cinnamyl-3,4-dihydroxy-a-cyanocinnamate (CDC) and Baicalein prevented platelet activation in a co-cultures of platelets and ASMC. The inhibitory effect of CDC and Baicalein on platelets was also registered in a pure platelet preparation. Specifically, the 12-LOX inhibitors reduced collagen-induced platelet aggregation both in the presence and absence of external added fibrinogen. Importantly, platelet-induced ASMC proliferation and ROS production generated during the platelet/ASMC interaction was significantly inhibited in the presence of 12-LOX inhibitors. In conclusion, our findings reveal that 12-LOX is crucial for the observed enhancement of ASMC proliferation in co-cultures of platelets and ASMC. The present result suggests that 12-LOX activity is important in the initial step of platelet/ASMC interaction and platelet activation. Such action of 12-LOX represents a potential important mechanism that may contribute to platelet-induced airway remodelling.

Av författaren/redakt...: Svensson Holm, A ...; Grenegård, Magnu ...; Ollinger, Karin; Lindström, Eva

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