Arachidonic Acid metabolites in the cardiovascular system: the role of lipoxygenase isoforms in atherogenesis with particular emphasis on vascular remodeling

Abstract

Vascular remodeling refers to lasting structural alterations in the vessel wall that are initiated in response to external and internal stimuli. These changes are distinct from acute functional responses of blood vessels when challenged by increased blood pressure, altered hemodynamics, or vasoactive mediators. In early atherogenesis, when lesion formation is starting to impact local hemodynamics, the vessel wall responds with outward vascular remodeling to maintain normal blood flow. However, inward remodeling may also occur during the time course of plaque formation, contributing to vascular stenosis. Lipoxygenases form a heterogeneous family of lipid-peroxidizing enzymes, which have been implicated in atherogenesis. Several lines of in vitro and in vivo evidence indicated their involvement in disease development, but the precise function of different lipoxygenase isoforms is still a matter of discussion. Vascular remodeling is an early response during plaque development; therefore, lipoxygenases may be involved in this process. Unfortunately, little is known about the potential role of lipoxygenase isoforms in vascular remodeling. This review will briefly summarize our knowledge of the role of lipoxygenases in vascular biology and will critically review the activities of the 3 most athero-relevant lipoxygenase isoforms in atherogenesis, with particular emphasis on vascular remodeling.