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.

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Acute vascular injury occurs in a number of important clinical contexts, including spontaneous disease-related events (e.g. plaque rupture, thrombosis) and therapeutic interventions such as angioplasty, stenting, or bypass surgery. Endothelial cell (EC) disruption exposes the underlying matrix, leading to a rapid deposition of platelets, coagulation proteins, and leukocytes. A thrombo-inflammatory response ensues characterized by leukocyte recruitment, vascular smooth muscle cell (VSMC) activation, and the elaboration of cytokines, reactive oxygen species and growth factors within the vessel wall. A resolution phase of vascular injury may be described in which leukocyte efflux, clearance of debris, and re-endothelialization occurs. VSMC migration and proliferation leads to the development of a thickened neointima that may lead to lumen compromise. Subsequent remodeling involves matrix protein deposition, and return of EC and VSMC to quiescence. Recent studies suggest that specialized proresolving lipid mediators (SPM) modulate key aspects of this response, and may constitute an endogenous homeostatic pathway in the vasculature. SPM exert direct effects on vascular cells that counteract inflammatory signals, reduce leukocyte adhesion, and inhibit VSMC migration and proliferation. These effects appear to be largely G-protein coupled receptor-dependent. Across a range of animal models of vascular injury, including balloon angioplasty, bypass grafting, and experimental aneurysm formation, SPM accelerate repair and reduce lesion formation. With bioactivity in the pM-nM range, a lack of discernible cytotoxicity, and a spectrum of vasculo-protective properties, SPM represent a novel class of vascular therapeutics. This review summarizes current research in this field, including a consideration of critical next steps and challenges in translation.

Objective Arterial stiffness and peripheral artery disease (PAD) are both associated with an elevated risk of major adverse cardiac events (MACE); however, the association between arterial stiffness and PAD is less well characterized. The goal of the present study was to examine the association between parameters of radial artery tonometry, a non-invasive measure of arterial stiffness, and PAD. Methods We conducted a cross-sectional study of 134 vascular surgery outpatients (controls=33, PAD=101) using arterial applanation tonometry. Central augmentation index normalized to 75bpm (central AIX) and peripheral augmentation index (peripheral AIX) were measured using radial artery pulse wave analysis (PWA). Pulse wave velocity (PWV) was recorded at the carotid and femoral arteries. PAD was defined as symptomatic claudication with an ankle-brachial index (ABI) of <0.9 or a history of peripheral revascularization. Controls had no history of atherosclerotic vascular disease and an ABI≥0.9. Results Among the 126 participants with high quality tonometry data, compared to controls (n=33), patients with PAD (n=93) were older, with higher rates of hypertension, hyperlipidemia, diabetes, and smoking (P<.05). Patients with PAD also had greater arterial stiffness as measured by central AIX, peripheral AIX, and PWV (P<.05). In a multivariable model, each 10-unit increase in central and peripheral AIX was associated with significantly increased odds of PAD (OR 2.1, 95% CI 1.1–3.9, P=.03 and OR 1.9, 95% CI 1.2–3.2, P=.01, respectively). Additionally, central and peripheral AIX were highly correlated (r(120)=.76, P<.001). Conclusions In a cross-sectional analysis, arterial stiffness as measured by the augmentation index is independently associated with PAD, even when adjusting for several atherosclerotic risk factors. Further prospective data is needed to establish whether radial artery tonometry could be a tool for risk stratification in the PAD population.

Background: The application of surface complexation models (SCMs) to natural sediments and soils is hindered by a lack of consistent models and data for large suites of metals and minerals of interest. Furthermore, the surface complexation approach has mostly been developed and tested for single solid systems. Few studies have extended the SCM approach to systems containing multiple solids.

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Background Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro‐resolving lipid mediators endogenously derived from omega‐3 fatty acids. We investigated the impact of a short‐course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers. Methods and Results This was a prospective, open‐label study of 5‐day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro‐resolving lipid mediators, and specialized pro‐resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte‐derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro‐resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD. Conclusions These data suggest that short‐term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro‐resolution phenotype in circulating leukocytes and monocyte‐derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02719665.