Cyclooxygenase exists in three
isoforms, COX-1 which is constitutively expressed across all tissues; COX-2
whose expression is induced by a number of physiological stimuli and COX-3 a
splice variant of COX-1, commonly called COX-1b.
Both COX-1 and COX-2 catalyse the
rate limiting reaction in the synthesis of prostaglandins, prostacyclins and
thromboxanes, with COX-2, the inducible isoform, favouring the production of
lipid mediators in a cell specific manner. Prostaglandins and prostacyclins are
mediators of inflammation and also play
a regulatory role in cardiovascular homeostasis. COX-2 is of interest from
a pharmacological perspective since non-steroidal anti-inflammatory drugs
(NSAIDs), including aspirin, are routinely used in the prevention of
cardiovascular disease and to alleviate pain associated with inflammatory
conditions.
COX-2 is involved in the
pathogenesis of inflammatory conditions including Type 2 diabetes mellitus and atherogenesis. Glucose mediated increases
in COX-2 expression result in reduced bioavailability of the vasodilator nitric
oxide and subsequent endothelial dysfunction. Nitric oxide has an additional
cardio protective role preventing the oxidation of low density lipoproteins.
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