Vascular Inflammation: Light at the End of the Tunnel
Aksam J Merched
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK.
Abstract:
Chronic inflammation of the artery wall can cause atherosclerosis, a major risk factor for heart disease and heart attack. Recent results indicate that acute inflammation does not simply passively resolve as previously assumed but is actively resolved by a homeostatic process controlled by bioactive lipid mediators produced by the lipoxygenases.
We found was that genetically increasing the production of the pro-resolution signals would cool down the inflammation and give the atherosclerosis a chance to slow down. However, genetically clamping down on these signals would fan the fire of inflammation and speed up the progression of atherosclerosis.
Lipoxygenase end-products such as lipoxins, protectins, resolvins and maresins exert potent anti-inflammatory actions. They reduce and/or limit the production of a large proportion of the pro-inflammatory cytokines produced by macrophages. They also stimulate the phagocytic activity of macrophages toward apoptotic cells, an important part of efferocytosis, a process that includes inhibition of inflammatory cell recruitment, promotion of inflammatory cell egress and clearance of apoptotic cells by phagocyte. Complementing their action on macrophages, theses lipid mediators also exhibit concerted inhibitory actions on adhesion molecule and chemokine expression by vascular endothelial cells, putting a brake on the recruitment of inflammatory cells, to allow the resolution phase to set in and give the vascular wall a chance to return to normalcy.
Our results underscore the potential of lipoxygenase products or their stable analogs as a novel class of anti-inflammatory drugs for the treatment of cardiovascular diseases.
