Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world.
Atherosclerosis followed by
thrombosis (
atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events.
Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and
proteins directly involved in these processes, traditional cardiovascular risk factors (
hyperlipidemia,
hypertension, smoking,
diabetes mellitus, sex, and age) remain the most useful predictor of disease.
Eicosanoids (20
carbon polyunsaturated fatty acid derivatives of
arachidonic acid and other
essential fatty acids) are emerging as important regulators of
cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/
COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing
eicosanoid signaling, have contributed to the lack of
therapies directed at the
eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the
eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the
eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between
eicosanoids and cardiovascular risk factors.