Temporal cascade of inflammatory cytokines and cell-type populations in monocyte chemotactic protein-1 (MCP-1)-mediated aneurysm healing

Abstract

Background We have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing. Objective To determine the temporal cascade and durability of aneurysm healing. Methods Murine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers. Results Aneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2–3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3–6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months. Conclusions The sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling.

Cannabidiol-Driven Alterations to Inflammatory Protein Landscape of Lipopolysaccharide-Activated Macrophages In Vitro May Be Mediated by Autophagy and Oxidative Stress

“…[88][89][90] Despite MCP-1 being generally described as a pro-inflammatory marker, several studies have also reported it to have a robust role in wound healing. [91][92][93] In contrast, RANTES, unlike MCP-1, is generally considered deleterious to the alternative noninflammatory roles of macrophages. 94,95 Therefore, its suppression appears to be desirable toward altering inflammatory polarization states.…”

Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing

“…Previous studies using MCP-1 KO mice in diabetic wound healing have shown reduced macrophage recruitment into the local environment ( 21 ). We have previously shown that recruitment of this macrophage axis is instrumental in our MCP-1 mediated aneurysm healing model ( 22 ). We have also previously shown that MCP-1 contributes to aneurysm healing by means of its downstream mediators ( 23 ).…”

Defective autophagy in vascular smooth muscle cells enhances the healing of abdominal aortic aneurysm

“…As a first step in the healing process (Hoh et al, 2018), circulating neutrophils infiltrate the area containing Azan staining the hematoma. Then, monocytes and macrophages are recruited to the site of the hematoma to remove extracellular matrix debris by phagocytosis.…”