| First Author | Gotha L | Year | 2014 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 307 |
| Issue | 3 | Pages | H337-45 |
| PubMed ID | 24858854 | Mgi Jnum | J:214299 |
| Mgi Id | MGI:5588741 | Doi | 10.1152/ajpheart.00654.2013 |
| Citation | Gotha L, et al. (2014) Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury. Am J Physiol Heart Circ Physiol 307(3):H337-45 |
| abstractText | Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits the smooth muscle cell (SMC) response to vascular injury. Hspg2(Delta3/Delta3) (MDelta3/Delta3) mice produce a mutant perlecan lacking the HS side chains. The objective of this study was to determine differences between these two types of perlecan in modifying SMC activities to the arterial injury response, in order to define the specific role of the HS side chains. In vitro proliferative and migratory activities were compared in SMC isolated from MDelta3/Delta3 and wild-type mice. Proliferation of MDelta3/Delta3 SMC was 1.5x greater than in wild type (P < 0.001), increased by addition of growth factors, and showed a 42% greater migratory response than wild-type cells to PDGF-BB (P < 0.001). In MDelta3/Delta3 SMC adhesion to fibronectin, and collagen types I and IV was significantly greater than wild type. Addition of DRL-12582, an inducer of perlecan expression, decreased proliferation and migratory response to PDGF-BB stimulation in wild-type SMC compared with MDelta3/Delta3. In an in vivo carotid artery wire injury model, the medial thickness, medial area/lumen ratio, and macrophage infiltration were significantly increased in the MDelta3/Delta3 mice, indicating a prominent role of the HS side chain in limiting vascular injury response. Mutant perlecan that lacks HS side chains had a marked reduction in the inhibition of in vitro SMC function and the in vivo arterial response to injury, indicating the critical role of HS side chains in perlecan function in the vessel wall. |
