Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice.
OBJECTIVE
Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)-deficient (apoE-/-) MMP-9-deficient (MMP-9-/-) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation.


RESULTS
Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE-/- MMP-9-/- mice had a significant reduction in intimal plaque length and volume compared with apoE-/- MMP-9+/+ mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow-derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE-/- MMP-9+/+ and apoE-/- MMP-9-/- mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development.


CONCLUSIONS
MMP-9 is derived from resident arterial cells and is required for early atherosclerotic plaque development and cellular accumulation in apoE-/- mice.
Choi
Eric T
ET
Department of Surgery, Washington University School of Medicine, St. Louis, Mo, USA. choie@msnotes.wustl.edu
Collins
Emily T
ET
Marine
Leopoldo A
LA
Uberti
Maria G
MG
Uchida
Hisashi
H
Leidenfrost
Jeremy E
JE
Khan
M Faisal
MF
Boc
Kenneth P
KP
Abendschein
Dana R
DR
Parks
William C
WC
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002339:Carotid Arteries / Q000201:enzymology / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology*; D019070:Cell Lineage; D008026:Ligation; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D001057:Apolipoproteins E; D020780:Matrix Metalloproteinase 9