Pro-resolving lipid mediators in vascular disease

Abstract

Unresolved inflammation is central to the pathophysiology of commonly occurring vascular diseases such as atherosclerosis, aneurysm, and deep vein thrombosis - conditions that are responsible for considerable morbidity and mortality. Surgical or catheter-based procedures performed on affected blood vessels induce acute-on-chronic inflammatory responses. The resolution of vascular inflammation is an important driver of vessel wall remodeling and functional recovery in these clinical settings. Specialized pro-resolving lipid mediators (SPMs) derived from omega-3 polyunsaturated fatty acids orchestrate key cellular processes driving resolution and a return to homeostasis. The identification of their potent effects in classic animal models of sterile inflammation triggered interest in their vascular properties. Recent studies have demonstrated that SPMs are locally synthesized in vascular tissues, have direct effects on vascular cells and their interactions with leukocytes, and play a protective role in the injury response. Early translational work has established the potential for SPMs as vascular therapeutics, and as candidate biomarkers in vascular disease. Further investigations are needed to understand the molecular and cellular mechanisms of resolution in the vasculature, to improve tools for clinical measurement, and to better define the potential for "resolution therapeutics" in vascular patients.

Association of Apolipoprotein E Polymorphisms with White Matter Lesions and Brain Atrophy

“…According to a previous report cardiovascular disease is associated with high blood lipid levels, type 2 diabetes and other metabolic diseases, such as hyperhomocysteinemia, hyperuricemia, hypertension. [20][21][22] In the present study, the metabolic index of the disease group (including WML, brain atrophy, cooccurrence of WML and brain atrophy) was higher than that of the healthy group, although most of the indicators were within the normal reference range. It is worth mentioning that the uric acid concentration in the disease group is higher than the normal range.…”

The resolution of inflammation through omega-3 fatty acids in atherosclerosis, intimal hyperplasia, and vascular calcification

“…Although the incidence of intimal hyperplasia after PCI drastically decreased after the introduction of drug-eluting stents, it remains a clinical problem in the pathophysiology of atherosclerosis and restenosis after CABG. Pathologically, intimal hyperplasia comes as an endpoint of the combination of different factors, such as VSMC proliferation and migration, immune cell infiltration into the vessel wall, and aberrant ECM deposition [73]. Hence, targeting proresolution pathways in this context would offer additional advantages in cardiovascular prevention.…”

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome

“…A novel superfamily of LMs that are called specialized proresolving mediators (SPMs), including lipoxins (LXs), ABBREVIATIONS: AA, arachidonic acid; COX, cyclooxygenase; cPLA 2 , cytosolic phospholipase A 2 ; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FLAP, 5-LOX-activating protein; HDHA, hydroxy DHA; HEPE, hydroxyeicosapentaenoic acid; HETE, hydroxyeicosatetraenoic acid; LM, lipid mediator; LOX, lipoxygenase; LT, leukotriene; LX, lipoxin; MaR, maresin; MRM, multiple reaction monitoring; NSAID, nonsteroidal anti-inflammatory drug; PD, protectin; PG, prostaglandin; pg, picogram; Rv, resolvin; SPM, specialized proresolving mediator; UPLC-MS-MS, ultraperformance liquid chromatography-tandem mass spectrometry resolvins (Rvs), maresins (MaRs), and protectins (PDs), that actively terminate inflammation and promote tissue regeneration are biosynthesized by COX and LOX pathways as well ( Fig. 1A) (2,7,8). Thus, COX and 5-LOX pathway inhibitors may interfere with beneficial SPM formation too.…”