Premium
Matrix Metaloproteinases (MMPs) are necessary for flow‐induced arterial remodeling
Author(s) -
Goel Mahesh,
Jiang Hui,
DiStasi Matthew R,
Galis Zorina S
Publication year - 2007
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.21.5.a193-c
Subject(s) - mmp2 , matrix metalloproteinase , bone remodeling , medicine , chemistry , in vivo , hemodynamics , mmp9 , ex vivo , endocrinology , cardiology , biology , downregulation and upregulation , biochemistry , cancer , gene , metastasis , microbiology and biotechnology
We studied the role of MMP‐2 and ‐9 in arterial remodeling in response to blood flow changes in vivo . Normal flow (NF), low flow (LF), and high flow (HF) were surgically produced in the mesenteric arterial bed of C57 Bl‐6 (WT), MMP9 or MMP2 null mice ( −/− ) and maintained for 3 (D3) or 14 days (D14). In situ external arterial diameter (ED) were recorded at the beginning (D0) and at the end (D3 or D14). Ex vivo measurements were performed on histological sections using Image J 1.34s and compared with one‐way ANOVA followed by post‐hoc analysis or Student's t test in JMP software. Pro‐ and active MMP‐2 and MMP‐9 were quantified using gelatin zymography and Quantity One 4.5.2 (Bio‐Rad). At D0, mean ED was similar for WT, MMP9 −/− and MMP2 −/− . In WT, compared to NF, the HF induced a significant mean ED increase, i.e. expansive remodeling and LF induced a mean ED decrease, i.e. constrictive remodeling by D14. In MMP9 −/− , LF induced significant inward remodeling at D3 (p<0.032), but mean ED were similar in NF, LF, or HF at D14, indicating remodeling impairment in both LF and HF. In MMP2 −/− the constrictive remodeling due to LF was statistically significant at both times (p<0.021) at D3; (p<0.031) at D14, but the outward remodeling in HF did not reach significance. Both MMPs contribute to flow‐induced arterial remodeling. MMP‐2 contributes to expansive remodeling, but lack of MMP‐2 did not impair constrictive remodeling, while MMP‐9 seems essential for both expansive and constrictive remodeling.