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Shear force regulates matrix metalloproteinase activity in human saphenous vein organ culture. J Surg Res 2001 Jan;95(1):67-72

Date

12/20/2000

Pubmed ID

11120638

DOI

10.1006/jsre.2000.6045

Scopus ID

2-s2.0-0035746742   13 Citations

Abstract

BACKGROUND: Development of vein graft intimal hyperplasia has been related both to shear force and to the activity of matrix metalloproteinases (MMPs). Little data are available regarding the effects of shear on MMP expression and activity. The aim of this study was to examine the relationship among shear force, metalloproteinase activity, and intimal thickening in human saphenous vein segments maintained in organ culture.

MATERIALS AND METHODS: Segments of human saphenous vein were cultured under static conditions, or perfused under low-flow and high-flow conditions in a perfusion apparatus for 7 days. Metalloproteinase levels and activities were measured using ELISA and substrate gel zymography, respectively. Intimal thickening was determined by morphometric analysis. Results were compared with control vein tissue, which was not subjected to organ culture, using a one-way ANOVA.

RESULTS: A 13% increase in proteolytic activity was noted on substrate gel zymography at 68-72 kDa in high-flow vein tissue. The protein content of MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 was increased in high-flow vein tissue by 21%, 126%, more than 100-fold, and 86%, respectively. In culture media bathing the outside of the vein, TIMP-2 was increased in high-flow specimens, while TIMP-1 was inversely related to flow rate. Intimal thickening was directly related to flow rates, and was progressively increased in the low-flow and high-flow groups by 3-fold and 4-fold, respectively.

CONCLUSIONS: Metalloproteinase levels in human saphenous vein cultures are related to shear force. MMP levels and activity correlate with the degree of intimal thickening. This model may provide a valuable tool for the analysis of physical forces and their influence on intimal thickening in human saphenous vein.

Author List

Patterson MA, Leville CD, Hower CD, Jean-Claude JM, Seabrook GR, Towne JB, Cambria RA

Author

Gary R. Seabrook MD Chief, Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Enzyme-Linked Immunosorbent Assay
Humans
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Organ Culture Techniques
Saphenous Vein
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc