Semicarbazide-Sensitive Amine Oxidase (SSAO) and Lysyl Oxidase (LOX) Association in Rat Aortic Vascular Smooth Muscle Cells
Vesna Manasieva,
Shori Thakur,
Lisa A. Lione,
Jessal Patel,
Anwar Baydoun,
John Skamarauskas
Affiliations
Vesna Manasieva
Imperial Biomedical Research Centre, Hammersmith Hospital, Department of Metabolism, Digestion and Reproduction, School of Medicine, Imperial College, London W12 0NN, UK
Shori Thakur
Centre for Health Services and Clinical Research, Basic and Clinical Science Unit, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
Lisa A. Lione
Centre for Health Services and Clinical Research, Basic and Clinical Science Unit, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
Jessal Patel
Centre for Health Services and Clinical Research, Basic and Clinical Science Unit, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
Anwar Baydoun
Leicester Institute of Pharmaceutical Innovation for Integrated Care (LIPIIC), Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
John Skamarauskas
Centre for Health Services and Clinical Research, Basic and Clinical Science Unit, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
Vascular smooth muscle cells (VSMCs) are the main stromal cells in the medial layer of the vascular wall. These cells produce the extracellular matrix (ECM) and are involved in many pathological changes in the vascular wall. Semicarbazide-sensitive amine oxidase (SSAO) and lysyl oxidase (LOX) are vascular enzymes associated with the development of atherosclerosis. In the vascular smooth muscle cells, increased SSAO activity elevates reactive oxygen species (ROS) and induces VSMCs death; increased LOX induces chemotaxis through hydrogen peroxide dependent mechanisms; and decreased LOX contributes to endothelial dysfunction. This study investigates the relationship between SSAO and LOX in VSMCs by studying their activity, protein, and mRNA levels during VSMCs passaging and after silencing the LOX gene, while using their respective substrates and inhibitors. At the basal level, LOX activity decreased with passage and its protein expression was maintained between passages. βAPN abolished LOX activity (** p p ## p p p p p p p p p p p p p #### p ### p # p < 0.05 for Si8 vs. Sictrl). These novel findings demonstrate a passage dependent decrease in LOX activity and increase in SSAO activity in rat aortic VSMCs and show an association between both enzymes in early passage rat aortic VSMCs, where LOX was identified as a regulator of SSAO activity, protein, and mRNA expression.