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Pro-resolving lipid mediators in vascular disease
Michael S. Conte, … , Melinda Schaller, Evan Werlin
Michael S. Conte, … , Melinda Schaller, Evan Werlin
Published August 31, 2018
Citation Information: J Clin Invest. 2018;128(9):3727-3735. https://doi.org/10.1172/JCI97947.
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Review Series

Pro-resolving lipid mediators in vascular disease

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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.

Authors

Michael S. Conte, Tejal A. Desai, Bian Wu, Melinda Schaller, Evan Werlin

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Figure 3

Perivascular delivery of RvD1 to rabbit vein grafts.

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Perivascular delivery of RvD1 to rabbit vein grafts.
(A and B) Images de...
(A and B) Images depict two methods of perivascular delivery of RvD1 to rabbit vein grafts (carotid interposition) using either a pluronic gel (A) or a PLGA film device (B). (C) PLGA films (“wraps”) were constructed using a thin bilayered design and loaded with 1 μg of RvD1; representative scanning electron microscopy of a film is shown. (D–G) Perivascular delivery of RvD1 via gel or wrap attenuated vein graft hyperplasia 28 days after implantation, whereas perivascular application of vehicle-loaded gels and wraps had no effect (elastin-stained sections). Adapted with permission from ref. 48.
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