Related Experiment Video
Updated: Jun 26, 2026
Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation
Tomohiro Aoki1, Hiroharu Kataoka, Ryota Ishibashi
1Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Insights
Monocyte chemoattractant protein-1 (MCP-1) is crucial for cerebral aneurysm (CA) formation by recruiting macrophages. Inhibiting MCP-1 may offer a new therapeutic strategy for preventing CA progression.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Molecular Medicine
Background:
- Chronic inflammation is implicated in cerebral aneurysm (CA) development.
- Macrophages infiltrate CA walls, expressing pro-inflammatory genes that drive CA progression.
- The precise mechanisms of monocyte/macrophage recruitment into CA walls are not fully understood.
Purpose of the Study:
- To investigate the role of monocyte chemoattractant protein-1 (MCP-1) in the formation and progression of cerebral aneurysms.
- To elucidate the molecular pathways, including nuclear factor-kappa B (NF-κB) activation, involved in MCP-1 expression in CAs.
Main Methods:
- Assessed MCP-1 expression in experimentally induced CAs using immunohistochemistry and Western blotting.
- Utilized MCP-1 knockout mice and a dominant-negative MCP-1 mutant (7ND) to examine MCP-1's role in CA formation.
- Analyzed MCP-1 expression in human CA tissues.
Main Results:
- MCP-1 expression was significantly upregulated in early-stage CA walls.
- MCP-1 knockout mice showed reduced CA formation and macrophage accumulation, with decreased matrix metalloproteinase (MMP) and inducible nitric oxide synthase (iNOS) expression.
- NF-κB activation was observed in MCP-1-expressing cells within CAs.
- Inhibition of MCP-1 activity with 7ND suppressed CA progression in rats.
- MCP-1 was detected in human CA walls.
Conclusions:
- MCP-1 is a key chemoattractant for monocytes/macrophages, playing a critical role in CA formation.
- MCP-1 expression in CA walls is regulated by NF-κB activation.
- MCP-1 presents a potential therapeutic target for preventing cerebral aneurysm progression.
Background And Purpose:
Recent studies have suggested that chronic inflammation actively participates in cerebral aneurysm (CA) formation. Macrophages accumulate in CA walls and express proinflammatory genes promoting CA progression, but the molecular mechanisms of monocyte/macrophage recruitment into CA walls remain to be elucidated.
Methods:
Monocyte chemoattractant protein-1 (MCP-1) expression in experimentally induced CAs was assessed by immunohistochemistry and Western blotting. The role of MCP-1 in CA formation was examined by MCP-1(-/-) mice and a plasmid DNA encoding a dominant negative mutant of MCP-1 (7ND). MCP-1 expression in human CAs was examined by immunohistochemistry.
Results:
MCP-1 expression was upregulated in aneurysmal walls at the early stage of CA formation. MCP-1(-/-) mice exhibited a significant decrease of CA formation and macrophage accumulation with decreased expression of matrix metalloproteinase-2, -9, and inducible nitric oxide synthase. Immunohistochemistry for the DNA binding form of nuclear factor-kappa B showed nuclear factor-kappa B activation in MCP-1-expressing cells. Blockade of MCP-1 activity by 7ND resulted in the inhibition of CA progression in rats. In human CAs, MCP-1 was also expressed in CA walls.
Conclusions:
These data suggest that MCP-1 plays a crucial role in CA formation as a major chemoattractant for monocyte/macrophage. MCP-1 expression in CA walls is induced through nuclear factor-kappa B activation. MCP-1 may be a novel therapeutic target of medical treatment preventing CA progression.
