title: Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function.
abstract: 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.
authors.affiliation: Division of Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University , Linköping , Sweden .
authors.forename: Ann-Charlotte B
authors.initials: AC
authors.lastname: Svensson Holm
authors.forename: Magnus
authors.initials: M
authors.lastname: Grenegård
authors.forename: Karin
authors.initials: K
authors.lastname: Ollinger
authors.forename: Eva G
authors.initials: EG
authors.lastname: Lindström
mesh_terms: D056151:Airway Remodeling; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004789:Enzyme Activation; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; D001092:Arachidonate 12-Lipoxygenase