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Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration
Asa Ström1, Anders I Olin, Anders Aspberg
1Department of Experimental Medical Science, Division of Vascular and Airway Research, Lund University, BMC, C12, S-221 84 Lund, Sweden. asa.strom@med.lu.se
Objective:
The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican/hyaluronan complexes, an ECM network that has been suggested to be important during tissue repair. In this study we have analysed the presence of fibulin-2 in two different models of murine vascular lesions. We have also examined how the fibulin-2/versican network influences SMC migration.
Methods:
Presence of fibulin-2 was analysed by immunohistochemistry in atherosclerotic aortas and in mechanically injured carotid arteries from mice. Fibulin-2 protein levels were also studied by Western blotting during rat aortic SMC phenotypic modulation in vitro. The importance of a fibulin-2/versican interaction for SMC migration was studied in the presence of two inhibiting peptides (FN III 3-5 and aggrecan C-type lectin-like domain).
Results:
Fibulin-2 is expressed in SMC rich regions of atherosclerotic lesions where it colocalises with versican and hyaluronan. It is also present in injury-induced vascular lesions and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro.
Conclusions:
Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation that regulates SMC migration during vessel wall repair.
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