Role of oxylipins in cardiovascular diseases

Abstract

Globally, cardiovascular diseases (CVDs) are the number one cause of mortality. Approximately 18 million people died from CVDs in 2015, representing more than 30% of all global deaths. New diagnostic tools and therapies are eagerly required to decrease the prevalence of CVDs related to mortality and/or risk factors leading to CVDs. Oxylipins are a group of metabolites, generated via oxygenation of polyunsaturated fatty acids that are involved in inflammation, immunity, and vascular functions, etc. Thus far, over 100 oxylipins have been identified, and have overlapping and interconnected roles. Important CVD pathologies such as hyperlipidemia, hypertension, thrombosis, hemostasis and diabetes have been linked to abnormal oxylipin signaling. Oxylipins represent a new era of risk markers and/or therapeutic targets in several diseases including CVDs. The role of many oxylipins in the progression or regression in CVD, however, is still not fully understood. An increased knowledge of the role of these oxygenated polyunsaturated fatty acids in cardiovascular dysfunctions or CVDs including hypertension could possibly lead to the development of biomarkers for the detection and their treatment in the future.

Intravenous fat induces changes in PUFA and their bioactive metabolites: Comparison between Japanese and Australian preterm infants

“…In the case of the PUFA, their FFA can subsequently be oxidized via enzymatic processes (lipoxygenase, cyclooxygenase and cytochrome P450) or via non-enzymatic free radical oxidation to produce a variety of biologically active molecules known as oxylipins [1]. These oxylipins play important roles with respect to inflammation and its resolution, platelet aggregation, vasodilatation and tissue repair processes [2][3][4].…”

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

“…The functions of oxylipins involve many aspects of body homeostasis including innate immunity, inflammation, cardiac function, blood coagulation, and vascular tone regulation (Nayeem, 2018). Compared to oxylipins derived from n-3 PUFAs (DHA, EPA), those derived from n-6 PUFAs (AA, LA) generally, but not always, exhibit pro-inflammatory, vasoconstrictive, and proliferative effects (Gabbs et al, 2015).…”

“…Once liberated by cytosolic phospholipase A2 (cPLA2) from membrane phospholipids, free PUFAs can be metabolized to form oxylipins via auto-oxidation or enzymes including cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP)-soluble epoxide hydrolase (sEH) pathways (Caligiuri et al, 2017). Given their short half-time and low content, oxylipins are found all over the tissues and support the body's homeostasis by regulating many important physiological processes such as inflammation, blood coagulation, and vascular function (Nayeem, 2018).…”

Bioactive Lipid Signaling in Cardiovascular Disease, Development, and Regeneration

“…Epoxyeicosatrienoic acids (EETs), a subfamily of eicosanoid-like molecules, can also be produced by the action of cytochrome P450 epoxygenase enzymes (see Figure 1 A). Eicosanoid-derived oxylipins are involved in cardiac injury and dysfunction [ 40 ], atherosclerosis [ 41 ], blood clotting and platelet aggregation [ 42 , 43 ], and blood pressure regulation [ 44 ].…”