Stretch-Induced Activation of the Transcription Factor Activator Protein-1 Controls Monocyte Chemoattractant Protein-1 Expression During Arteriogenesis

Cerebral, coronary, and peripheral artery diseases combined represent the most frequent cause of death in developed nations. The underlying progressive occlusion of large conductance arteries can partially be compensated for by transformation of preexisting collateral arterioles to small artery bypa...

Full description

Saved in:
Bibliographic Details
Published in:Circulation research 2008-08, Vol.103 (5), p.477-484
Main Authors: Demicheva, Elena, Hecker, Markus, Korff, Thomas
Format: Article
Language:English
Subjects:
Animals
Arterioles - growth & development
Arterioles - physiology
Biological and medical sciences
Chemokine CCL2 - genetics
Chemokine CCL2 - metabolism
Collateral Circulation - physiology
Ear - blood supply
Femoral Artery - physiology
Fundamental and applied biological sciences. Psychology
Gene Expression - physiology
Hindlimb - blood supply
Ligation
Male
Mice
Mice, Inbred Strains
Models, Animal
Monocytes - physiology
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - physiology
Neovascularization, Physiologic - physiology
Stress, Mechanical
Transcription Factor AP-1 - metabolism
Up-Regulation - physiology
Vertebrates: cardiovascular system
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cerebral, coronary, and peripheral artery diseases combined represent the most frequent cause of death in developed nations. The underlying progressive occlusion of large conductance arteries can partially be compensated for by transformation of preexisting collateral arterioles to small artery bypasses, a process referred to as arteriogenesis. Because biomechanical forces have been implicated in the initiation of arteriogenesis, we have investigated the mechanosensitive expression of a pivotal proarteriogenic molecule, monocyte chemoattractant protein (MCP)-1, which governs the recruitment of circulating monocytes to the wall of the remodeling collateral arterioles. Using a new ear artery ligation model and the classic hindlimb ischemia model in mice, we noted that MCP-1 expression is significantly increased in collateral arterioles undergoing arteriogenesis already 24 hours after its onset. By mimicking proarteriogenic perfusion conditions in small mouse arteries, we observed that MCP-1 expression is predominantly upregulated in the smooth muscle cells, which solely sense changes in circumferential wall tension or stretch. Subsequent analyses of cultured endothelial and smooth muscle cells confirmed that cyclic stretch but not shear stress upregulates MCP-1 expression in these cells. Blockade of the mechanosensitive transcription factor activator protein-1 by using a specific decoy oligodeoxynucleotide abolished this stretch-induced MCP-1 expression. Likewise, topical administration of the decoy oligodeoxynucleotide to the mouse ear abrogated arteriogenesis through downregulation of MCP-1 expression and monocyte recruitment. Collectively, these findings point toward a stretch-induced activator protein-1–mediated rise in MCP-1 expression in vascular smooth muscle cells as a critical determinant for the initiation of arteriogenesis.
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.108.177782