Targeting leukotriene biosynthesis to prevent atherosclerotic cardiovascular disease
- PMID:38800614
- PMCID: PMC11126214
Targeting leukotriene biosynthesis to prevent atherosclerotic cardiovascular disease
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide. As such, new treatments are needed to prevent the onset and progression of atherosclerosis to improve outcomes in patients with coronary, cerebrovascular, and peripheral arterial disease. In this regard, inflammation is known to be a critical driver of atherosclerosis formation and progression, thus it is a viable target for vascular protection in patients at risk of developing ASCVD. Leukotrienes, key pro-inflammatory lipid mediators derived from arachidonic acid, are associated with atheroma inflammation and progression. Genetic mutations in key components of the leukotriene synthesis pathway, such as 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP), are associated with an increased risk of cardiovascular disease, and pharmacological inhibition of 5-LO and FLAP has been reported to prevent atheroma formation in pre-clinical and early clinical studies. In this article, we provide an overview of these studies and highlight the therapeutic potential of targeting leukotriene synthesis to prevent atheroma inflammation and progression and improve outcomes in patients at risk of ASCVD.
Keywords: 5-lipoxygenasE; 5-lipoxygenase-activating protein; Atherosclerosis; Cardiovascular Diseases; Leukotrienes.
Conflict of interest statement
XMW, WB, LB and DJH declare no conflict of interest. MC has received funding from Astra Zeneca for the PASSIVATE trial. DJH is an Editor for Conditioning Medicine, and he has not participated at any level in the editorial review of this manuscript.
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