Lipoxygenases Prostaglandin H Synthases and Cytochrome P450s in endothelium

Endothelial cells (ECs) express several enzymes that oxidize unsaturated lipid to signaling mediators. These include both constitutive and inducible isoforms of prostaglandin H synthases (PGHS), lipoxygenases (LOX), and cytochrome P450 (CYP), with the levels of expression and isoform type being dependent on the tissue of origin and inflammatory state of the cells. The healthy endothelium generates a number of oxidized lipid mediators including prostacyclin (PGI2) and epoxyeicosatetraenoic acids (EET). Following an inflammatory challenge, the properties of the endothe-lium alter with a switch from generation of vasoprotective mediators, to formation of factors that can potentiate the inflammatory response, including cysteinyl leukotrienes and hydroxyeicosatetraenoic acids (HETEs) (Figure 1). The predominant substrate utilized by all these pathways is arachi-donate, hydrolyzed from the sn2 position of phospholipids by phospholipase A2, in response to agonist activation. Following release, it undergoes enzymatic oxidation and isomerization forming a complex variety of signaling mediators that either are released to signal in adjacent cells or signal intracellularly in the endothelium itself. The following sections will describe each signaling pathway focusing in particular on their expression and function in the microvas-cular endothelium and biological actions of their lipid products on EC themselves.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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