Premium
Slingshot‐isoform specific regulation of cofilin activation during VSMC migration and neointima formation following vascular injury
Author(s) -
Torres Rebecca A.,
Drake Douglas A.,
Solodushko Viktoryia,
Jadhav Rashmi,
Smith Erika S.,
Rocic Petra,
Weber David S.
Publication year - 2010
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.24.1_supplement.790.7
Subject(s) - neointima , cofilin , vascular smooth muscle , microbiology and biotechnology , chemistry , biology , medicine , endocrinology , actin cytoskeleton , cell , biochemistry , cytoskeleton , smooth muscle , restenosis , stent
Vascular smooth muscle cell (VSMC) migration is a vital component of neointima formation following vascular injury. Our findings demonstrate that cofilin is critical for VSMC migration. Cofilin activation (dephosphorylation) at Ser3 is regulated by the Slingshot (SSH) phosphatase family. Each of the three SSH isoforms (1, −2, −3) is expressed in both cultured VSMCs and carotid artery tissue. In vitro studies examining SSH isoform regulation of cofilin activation during migration revealed that only SSH1 regulates of PDGF‐induced VSMC migration. Thus, we hypothesized that SSH1‐dependent cofilin activation is a key mechanism regulating VSMC migration during neointima formation following vascular injury. To test this, rat carotid arteries were injured with a Fogarty 2F catheter. The degree of vascular injury was quantified 14 days post injury by comparing wall thickness, cross‐sectional wall area and media/intima ratio in H&E stained cross sections. Immunoblot analysis revealed that both cofilin and SSH1 expression were elevated at 4, 7 and 14 days post injury (vs. non‐injured). Moreover, IHC staining of injured arteries confirmed that localization of both cofilin and SSH1 expression was primarily in the neointima. Taken together, our studies suggest that SSH1‐dependent cofilin activation during VSMC migration potentially contributes to neointima formation following vascular injury in vivo. NIH HL084159