Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution.

Autor: Nguyen KP; Division of Vascular Surgery, Oregon Health and Science University, Portland, OR, United States of America., McGilvray KC; Orthopaedic Bioengineering Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, Fort Collins, CO, United States of America., Puttlitz CM; Orthopaedic Bioengineering Research Laboratory, Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, Fort Collins, CO, United States of America., Mukhopadhyay S; Center for Vascular and Inflammatory Diseases and Division of Vascular Surgery, University of Maryland, Baltimore, MD, United States of America., Chabasse C; Center for Vascular and Inflammatory Diseases and Division of Vascular Surgery, University of Maryland, Baltimore, MD, United States of America., Sarkar R; Center for Vascular and Inflammatory Diseases and Division of Vascular Surgery, University of Maryland, Baltimore, MD, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2015 Sep 25; Vol. 10 (9), pp. e0139145. Date of Electronic Publication: 2015 Sep 25 (Print Publication: 2015).
DOI: 10.1371/journal.pone.0139145
Abstrakt: Objective: Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall.
Methods and Results: The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice.
Conclusions: MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution.
Databáze: MEDLINE
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