Eicosanoids represent a diverse family of lipid mediators with fundamental roles in
controlling physiology and disease.
Within the eicosanoid super family are
prostanoids, which are specifically derived from arachidonic acid by the enzyme
cyclooxygenase
(C
OX)
.
COX
has two isoforms;
COX
-
1 and
COX
-
2.
COX
-
2 is the
therapeutic target for the nonsteroidal anti
-
inflammatory drug (NSAID) class of pain
medications. Of the prostanoids,
prostacyclin, first discovered by Sir Professor John
Vane in 1976
,
remains amongs
t the best studied and retains an impressive pedigree
as on
e
the bodies fundamental cardiovascular protective pathways.
Since
this time
,
we have learnt much about how eicosanoids,
COX
enzymes and prostacyclin function
in the cardiovascular system which has allowed us to, for example, harness the
power of prostacyclin as therapy to treat pulmonary
arterial
hypertension and
peripheral vascular disease.
However, there remain many unanswer
ed questions in
our basic understanding of the pathways and how they can be used
to improve
human health. Perhaps the most important
and
controversial
outstanding
question
in the field remains
;
‘
how
do NSAIDs
produce their much publicized cardiovascular
si
de effects
?’
This review
summarises the history, bio
logy and cardiovascular
function of key eicosanoids with particular focus on prostacyclin and other
COX
products and discusses how our knowledge of these pathways can
applied in future
drug discovery and
be used to explain the cardiovascular side effects of
NSAIDs.