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VOL. 74 (4) PROSTANOIDS ACTIONS IN CARDIOVASCULAR...

inhibition of COX-2 lead to a reduction in the production of the
vasodilator PGI2 whereas production of the vasoconstrictor and pro-
aggregatory TXA2, mostly COX-1–dependent, remains unaffected. Thus,
disruption of the physiological balance between TXA2 and PGI2
accelerates atherosclerosis and increases the risk of thrombosis and other
cardiovascular complications (Figure 3).

FIGURE 3.- The balance hypothesis for the cardiovascular effects of NSAIDs.
Cardiovascular homeostasis is controlled by the balance between COX-1 –dependent
production of TXA2 by platelets and COX-2 –mediated PGI2 (prostacyclin) production

by endothelial cells. Whereas TXA2 function as a potent platelet activator and
vasoconstrictor, PGI2 inhibits platelet aggregation and thrombosis. Classical non-
selective NSAIDs reduce the production of TXA2 by platelets through their ability to
inhibit COX-1 activity thus displaying anti-thrombotic properties. In contrast, COX-2
selective NSAIDs reduce PGI2 formation by endothelial cells consequently disturbing the

equilibrium between TXA2 and PGI2 and potentially favouring pro-thrombotic
cardiovascular events.

Nevertheless, the mechanisms underlying the pathogenesis of
cardiovascular complications upon NSAIDs administration remain to be
clarified as the TXA2/PGI2 balance theory is somewhat simple and it does
not consider some important clinical and experimental evidences as the
increased risk of cardiovascular events by some non-selective NSAIDs,
the contribution of other prostanoids to the overall effect in
cardiovascular physiopathology, and the COX-2 independent effects of
NSAIDs. In this sense, a more profound knowledge of the complex

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