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Perfusion Restoration Following Femoral Artery Occlusion is Markedly Inhibited in Mice with MMP9 Deficient Bone‐Marrow Derived Cells
Author(s) -
Meisner Joshua K,
Bajikar Sameer S,
Price Richard J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.774.8
Subject(s) - arteriogenesis , mmp9 , bone marrow , perfusion , hindlimb , revascularization , femoral artery , medicine , ligation , ischemia , anatomy , microbiology and biotechnology , chemistry , biology , downregulation and upregulation , biochemistry , myocardial infarction , gene
Numerous studies have shown bone marrow‐derived cells (BMCs) play a critical role in orchestrating arteriogenesis. Bakker et al (2008) recently showed that BMCs, monocytes in particular, orchestrate arteriogenesis by allowing for outward or inward remodeling depending on arterial tone. We propose that one mechanism through which BMCs perform this accommodating function is through the secretion of matrix metalloproteases, resulting in a number of actions such as the breakdown of extracellular matrix (ECM) components. In particular, MMP9 is known to play an important role in vascular remodeling. Therefore, we hypothesized that the knockout of MMP9 specifically in BMCs will decrease arteriogenesis in a mouse model of hindlimb ischemia. To test our hypothesis, we created bone marrow (BM) chimeric mice by lethally irradiating host wild‐type (WT) mice and then reconstituting them with BM from either WT (WT→WT, control) or MMP9 −/− (MMP9→WT) mice. Femoral artery ligation was then performed to stimulate arteriogenesis in the vessels of the upper hindlimb. Leg revascularization was monitored non‐invasively using laser Doppler perfusion imaging over the course of 14 days. MMP9→WT mice show a significant decrease in revascularization versus control mice at all time points after day 2. These and additional preliminary findings in collateral vessel cross‐sections and whole mounts demonstrate that BMC‐specific MMP9 expression is critical for normal perfusion restoration through arteriogenesis. Supported by NIH R01‐HL074082‐04.