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Review
. 2020:159:170-179.
doi: 10.1016/j.addr.2020.07.011. Epub 2020 Jul 19.

Specialized pro-resolving lipid mediators in cardiovascular disease, diagnosis, and therapy

Alexander S Kim  1 , Michael S Conte  2
Affiliations
Review

Specialized pro-resolving lipid mediators in cardiovascular disease, diagnosis, and therapy

Alexander S Kim et al. Adv Drug Deliv Rev. 2020.

Abstract

Persistent inflammation is the key aggravator in many cardiovascular diseases, including atherosclerosis, aneurysm, injury/reperfusion, thrombosis, and neointimal hyperplasia following surgical or percutaneous interventions. Resolution is an active process orchestrated by specialized pro-resolving lipid mediators (SPMs) which tamp down acute inflammatory signals, promote healing and facilitate a return to homeostasis. SPMs are endogenously derived from poly-unsaturated fatty acids, and their biologic activity is mediated via specific G-protein coupled receptor binding. The potency of SPM in regulating the inflammatory response has encouraged investigation into their therapeutic and diagnostic use in cardiovascular pathologies. Herein we describe the translational groundwork which has established the synthesis and interactions of SPM in cardiovascular and hematologic cells, the therapeutic effects of SPM in animal models of cardiovascular disease, and some early technologies that harness and attempt to optimize SPM delivery and "resolution pharmacology". Further studies are required to precisely determine the mechanisms of resolution in the cardiovascular system and to determine the clinical settings in which SPM can be utilized to optimize patient outcomes.

Keywords: Atherosclerosis; Cardiovascular disease; Drug delivery; Inflammation; Intimal hyperplasia; Lipid mediators; Resolution; Resolvins.

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Conflict of interest statement

Declaration of Competing Interest MSC is co-inventor on patents (USPTO 9,463,177; 10,111,847) assigned to Regents of the University of California and Brigham and Women's Hospital. MSC is a co-founder of VasaRx.

Figures

Figure 1:
Figure 1:
Local delivery of SPM to improve vascular graft healing. Bypass grafts are subject to an acute inflammatory response that can lead to intimal hyperplasia, particularly at the anastomoses. The cartoon (A) depicts two methods of perivascular delivery of SPM using a gel or a thin film device, illustrated in panel B as applied to rabbit vein grafts in-vivo. PLGA films (“wraps”) were created with a thin bi-layered design for unidirectional release and loaded with 1 μg of RvD1. Delivery of RvD1 with gel or wrap decreased rabbit vein graft hyperplasia at 28 days post-implantation, while vehicle controls had no effect (C,D). Adapted with permission from ref
See this image and copyright information in PMC

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