Abstract
Angiotensin II (AngII) infusion promotes macrophage infiltration into the aortic wall
resulting in several forms of vascular pathology. To determine the causal role of
macrophages in these vascular diseases, we used osteopetrotic (op) male mice in which a natural mutation ablates production of M-CSF and results in
severe depletion of monocytes. AngII infusion into apoE−/− mice resulted in increased
atherosclerosis that was attenuated in op mice. AngII infusion in op mice unexpectedly produced grossly discernable thickening of the proximal thoracic
aorta characterized by intra-mural hematoma. This pathology was also observed in apoE+/+ × op male mice, and therefore, independent of hyper-lipidemia. No perceptible structural
properties of aortas from op mice could be discerned prior to AngII infusion. Regional effects in the contractile
response to phenylephrine were noted in aortic rings with enhanced responsivity in
the upper thoracic aortas of op mice compared to those from +/+ mice. No differences in contractile response were
noted in aortic rings from the lower thorax. In conclusion, deficiency of M-CSF attenuated
AngII-induced atherosclerosis but led to an unanticipated pathology of intra-laminar
hemorrhage in the upper aortic regions.
Abbreviations:
AngII (angiotensin II), AAAs (abdominal aortic aneurysms), M-CSF (macrophage-colony stimulating factor), PE (phenylephrine)Keywords
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Article info
Publication history
Published online: September 08, 2005
Accepted:
August 1,
2005
Received in revised form:
July 29,
2005
Received:
June 18,
2005
Identification
Copyright
© 2005 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
