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TIMP‐1 is increased by shear stress in the skeletal muscle microvasculature
Author(s) -
Uchida Cassandra,
Milkiewicz Malgorzata,
Fudalewski Tom,
Gee Eric,
Haas Tara L.
Publication year - 2008
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.22.1_supplement.925.8
Subject(s) - extracellular matrix , matrix metalloproteinase , downregulation and upregulation , proteolysis , shear stress , angiogenesis , chemistry , endocrinology , extracellular , medicine , enzyme , materials science , biochemistry , composite material , gene
Luminal splitting via internal division of capillaries is a form of angiogenesis caused by increased shear stress. A feature of luminal splitting is a lack of extracellular matrix proteolysis, which correlates with a decreased production of matrix metalloproteinase‐2 (MMP‐2). We hypothesized that the MMP inhibitor, tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1), is upregulated in response to shear stress. TIMP‐1 mRNA expression increased 3.8‐fold in the EDL of prasozin‐treated rats (p<0.05, n=4). Skeletal muscle endothelial cells were exposed to 2, 4, or 24 hours of shear stress (12 dyne/cm 2 ). TIMP‐1 mRNA expression increased 7.0 and 9.0‐fold in cells after 2 and 24 hours of exposure to shear stress respectively (p<0.05, n=3), and TIMP‐1 protein increased 1.5 and 2.2‐fold after 2 and 24 hours of shear stress (p<0.05, n=3). TIMP‐1‐mediated inhibition of MMP‐2 also was increased 1.5 and 1.3‐fold after 2 and 24 hours of shear stress (n=2 and p<0.05, n=3 respectively). Our results show that TIMP‐1 is upregulated by shear stress, and suggest a mechanism for the absence of extracellular matrix proteolysis observed during luminal splitting. Funded by the Heart and Stroke Foundation of Canada.