Hemodynamic forces regulate mural macrophage infiltration in experimental aortic aneurysms.
Blood flow (BF) and wall shear stress (WSS) influence reactive oxygen species production and oxidative stress in abdominal aortic aneurysm (AAA) disease. To gain further insight into the mechanisms of hemodynamic influences on AAA inflammation, we examined aneurysm macrophage density, chemotaxis and survival under varying aortic flow conditions. Rat AAAs were created via porcine pancreatic elastase (PPE) infusion. In selected cohorts, AAA flow was increased via left common femoral arteriovenous fistula (AVF) creation (HF-AAA) or decreased by left common iliac ligation (LF-AAA). WSS was highest in HF-AAA (10.4 +/- 2.3 dyn/cm(2) vs. 2.4 +/- 0.4 and 0.5 +/- 0.2 for NF- and LF-AAA, respectively, P < 0.001) 7 days after PPE infusion, with reduced medial macrophage density and increased apoptosis. Adventitial macrophage density was not significantly influenced by flow. Monocyte chemoattractant protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression correlated with observed macrophage densities in the media and adventitia. Luminal flow conditions regulate AAA inflammation in part via influences on medial macrophage density. Hemodynamic forces may modulate AAA inflammation and diameter enlargement via direct regulation of intimal macrophage adhesion, transmural migration or survival.
Sho
Eiketsu
E
Division of Vascular Surgery, Stanford University, Palo Alto, CA 94304, USA.
Sho
Mien
M
Hoshina
Katsuyuki
K
Kimura
Hideo
H
Nakahashi
Takeshi Ken
TK
Dalman
Ronald L
RL
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006439:Hemodynamics; D018056:Hemorheology; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010196:Pancreatic Elastase / Q000633:toxicity; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033081:Shear Strength
D018932:Chemokine CCL2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010196:Pancreatic Elastase