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Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Örebro University, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.ORCID iD: 0000-0003-4075-159X
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
2014 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 25, no 2, 111-117 p.Article in journal (Refereed) Published
Abstract [en]

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-α-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.

Place, publisher, year, edition, pages
Informa Healthcare, 2014. Vol. 25, no 2, 111-117 p.
Keyword [en]
12-lipoxygenase, airway remodelling, airway smooth muscle, platelet-induced proliferation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-99371DOI: 10.3109/09537104.2013.783688ISI: 000331905100006PubMedID: 23534390OAI: oai:DiVA.org:liu-99371DiVA: diva2:656695
Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2017-12-06Bibliographically approved

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Svensson Holm, Ann-CharlotteGrenegård, MagnusOllinger, KarinLindström, Eva

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