The Link between Prostanoids and Cardiovascular Diseases

Abstract

Cardiovascular diseases are the leading cause of global deaths, and many risk factors contribute to their pathogenesis. In this context, prostanoids, which derive from arachidonic acid, have attracted attention for their involvement in cardiovascular homeostasis and inflammatory processes. Prostanoids are the target of several drugs, but it has been shown that some of them increase the risk of thrombosis. Overall, many studies have shown that prostanoids are tightly associated with cardiovascular diseases and that several polymorphisms in genes involved in their synthesis and function increase the risk of developing these pathologies. In this review, we focus on molecular mechanisms linking prostanoids to cardiovascular diseases and we provide an overview of genetic polymorphisms that increase the risk for cardiovascular disease.

Keywords: arachidonic acid pathway; cardiovascular diseases; genetic polymorphisms; inflammation; prostanoids.

Figure 1

Arachidonic acid metabolism. An overview of the AA pathway, starting from its cleavage from cellular membranes via the phospholipase A2 enzymes, which leads to four classes of eicosanoids: prostanoids, epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and leukotrienes. Eicosanoids are synthesized by three classes of enzymes: cyclooxygenases, lipoxygenases, and CYP450 enzymes, which includes both ω-hydroxylases and epoxygenases.

Figure 2

Responses elicited in different cell types by interaction between prostaglandin D2 and distinct receptors. → denotes induction; ⊣ denotes inhibition.

Figure 3

Responses elicited in different cell types by interaction between prostaglandin 15d-PGJ2 and distinct receptors. → denotes induction; ⊣ denotes inhibition.

Figure 4

Responses elicited in different cell types by interaction between prostaglandin F2α and FP receptor. → denotes induction; ⊣ denotes inhibition.

Figure 5

Responses elicited in different cell types by interaction between prostaglandin E2 and EP1 and EP3 receptors. → denotes induction; ⊣ denotes inhibition.

Figure 6

Responses elicited in different cell types by interaction between prostaglandin E2 and EP2 and EP4 receptors. → denotes induction; ⊣ denotes inhibition.

Figure 7

Responses elicited in different cell types by interaction between thromboxane A2 and TP receptor isoforms. → denotes induction.

Figure 8

Responses elicited in different cell types by interaction between prostacyclin I2 and IP receptor. → denotes induction; ⊣ denotes inhibition.