2 research outputs found
An Epoxyisoprostane Is a Major Regulator of Endothelial Cell Function
The goal of these studies was to
determine the effect of 5,6-epoxyisoprostane,
EI, on human aortic endothelial cells (HAEC). EI can form as a phospholipase
product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-<i>sn</i>-glycero-3-phosphocholine, PEIPC, a proinflammatory molecule that
accumulates in sites of inflammation where phospholipases are also
increased. To determine the effect of EI on HAEC, we synthesized several
stereoisomers of EI using a convergent approach from the individual
optically pure building blocks, the epoxyaldehydes <b>5</b> and <b>6</b> and the bromoenones <b>14</b> and <b>16</b>.
The desired stereoisomer of EI can be prepared from these materials
in only six operations, and thus, large amounts of the product can
be obtained. The trans/trans isomers had the most potent activity,
suggesting specificity in the interaction of EI with the cell surface.
EI has potent anti-inflammatory effects in HAEC. EI strongly inhibits
the production of MCP-1, a major monocyte chemotactic factor, and
either decreases or minimally increases the levels of 10 proinflammatory
molecules increased by PEIPC. EI also strongly down-regulates the
inflammatory effects of IL-1β, a major inflammatory cytokine.
Thus EI, a hydrolytic product of PEIPC, has potent anti-inflammatory
function