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An eicosanoid-centric view of atherothrombotic risk factors

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Abstract

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.

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Acknowledgments

We are grateful for our outstanding eicosanoid centric colleagues who have collaborated with us in our studies on eicosanoids and cardiovascular disease. In pursuing our studies, we are also grateful for generous funding from NIH (NHLBI) and the American Heart Association. This review is dedicated to the memory of Har Gobind Khorana (1922–2011) a brilliant scientist and mentor without whom many of these studies would not have been possible.

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  1. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT, 06511, USA

    Scott Gleim, Jeremiah Stitham, Wai Ho Tang, Kathleen A. Martin & John Hwa

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  1. Scott Gleim
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  2. Jeremiah Stitham
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Correspondence to John Hwa.

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Gleim, S., Stitham, J., Tang, W.H. et al. An eicosanoid-centric view of atherothrombotic risk factors. Cell. Mol. Life Sci. 69, 3361–3380 (2012). https://doi.org/10.1007/s00018-012-0982-9

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  • DOI: https://doi.org/10.1007/s00018-012-0982-9

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