Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration.
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.
Ström
Asa
A
Department of Experimental Medical Science, Division of Vascular and Airway Research, Lund University, BMC, C12, S-221 84 Lund, Sweden. asa.strom@med.lu.se
Olin
Anders I
AI
Aspberg
Anders
A
Hultgårdh-Nilsson
Anna
A
D053674:Aggrecans; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000032:analysis / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053675:Versicans
C508320:Acan protein, mouse; C508321:Acan protein, rat; D053674:Aggrecans; D001057:Apolipoproteins E; D002135:Calcium-Binding Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010455:Peptides; D011973:Receptors, LDL; C508323:Vcan protein, mouse; C508324:Vcan protein, rat; C084612:fibulin 2; D053675:Versicans; D006820:Hyaluronic Acid