Recent Insights into the Role of Prostanoids in Atherosclerotic Vascular Disease

Abstract

Atherosclerosis is characterized by chronic inflammation and enrichment of inflammatory cells in the vessel wall. Acute inflammation can lead to damaged endothelium triggering the coagulation cascade and thrombus formation. Likewise, the clotting cascade may elicit an inflammatory response. The vascular endothelium regulates vascular tone, permeability, inflammation, thrombosis, and coagulation. Dysfunction of the vascular endothelium can promote atherosclerotic disease processes. Prostanoids (prostaglandins, thromboxane, and prostacyclin) have been established as inflammatory mediators in vascular endothelial function and there continues to be growing insights into their role in atherosclerotic disease. This review examines the role of prostanoids as paracrine inflammatory mediators of atherosclerotic vascular disease, highlighting the relevant physiology of eicosanoid production and endothelial dysfunction. We consider the role of prostanoids in systemic diseases associated with high cardiovascular morbidity and mortality, including diabetes mellitus, coronary artery disease, peripheral arterial disease, rheumatologic disorders, and dyslipidemia. We present emerging evidence that cardio-protective and lipid lowering medications, such as irbesartan and simvastatin may exert their effects via prostanoid mediated pathways. Both serum and urinary prostanoids may be utilized as diagnostic predictors of disease; for example 8-iso-PGF(2alpha) in the serum has recently been reported as an independent predictor of symptomatic peripheral arterial disease. In addition, we discuss current recommendations on established therapeutic uses of prostanoids for atherosclerotic diseases, such as the use of PGE(1) for the treatment of peripheral arterial disease. Finally, we investigate original therapeutic modalities of various prostanoids involved in the aforementioned diseases.

Redox-active antioxidant modulation of lipid signaling in vascular endothelial cells: vitamin C induces activation of phospholipase D through phospholipase A2, lipoxygenase, and cyclooxygenase

“…AA metabolites including the LOX-and COX-generated prostanoids (PGs, thromboxane, and prostacyclin), hydroperoxy and hydroxy metabolites, and LTs have been identified as important inflammatory mediators in vascular endothelial dysfunction and atherosclerosis [41,42]. Both the isoforms of COX, COX-1 and COX-2, convert AA into prostaglandin H 2 (PGH 2 ), which acts as a substrate for further metabolic conversion into TXA 2 , prostacyclin (PGI 2 ), and PGE 2 in vascular cells [44,45].…”

Changes in Plasma Levels of Vasoactive Factors in Patients Undergoing Abdominal Surgery

“…TXA 2 is mainly produced in platelets and is a potent vasoconstrictor and platelets aggregating agent [31] [32]. It can also be synthesized by other cell types [33] [34]. Inhibition of TXA 2 synthesis decreased ischemic events in clinical trials, suggesting an important role for TXA 2 in in vivo regulation of hemostasis and thrombosis [35].…”

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions

“…In an animal model of hypercholesterolemia (ApoE/LDLR-/- mice), MNA was found to increase the Tyr/Phe ratio and improve the endothelial function [ 198 ]. Additionally, MNA promotes prostacyclin (PGI2) secretion by endothelial cells, preventing platelet aggregation, smooth muscle cell proliferation, and leukocyte adhesion to the endothelium [ 199 , 200 ]. MNA also demonstrates anti-inflammatory effects and enhances the endothelial NO and PGI2 levels, as evidenced by studies indicating that MNA administration does not diminish the reduction in inflammatory cytokines in macrophages [ 201 ].…”