| First Author | Zimmerman KA | Year | 2015 |
| Journal | J Vasc Res | Volume | 52 |
| Issue | 5 | Pages | 306-20 |
| PubMed ID | 26910059 | Mgi Jnum | J:303074 |
| Mgi Id | MGI:6511548 | Doi | 10.1159/000443884 |
| Citation | Zimmerman KA, et al. (2015) Calreticulin Regulates Neointima Formation and Collagen Deposition following Carotid Artery Ligation. J Vasc Res 52(5):306-20 |
| abstractText | BACKGROUND/AIMS: The endoplasmic reticulum (ER) stress protein, calreticulin (CRT), is required for the production of TGF-beta-stimulated extracellular matrix (ECM) by fibroblasts. Since TGF-beta regulates vascular fibroproliferative responses and collagen deposition, we investigated the effects of CRT knockdown on vascular smooth-muscle cell (VSMC) fibroproliferative responses and collagen deposition. METHODS: Using a carotid artery ligation model of vascular injury, Cre-recombinase-IRES-GFP plasmid was delivered with microbubbles (MB) to CRT-floxed mice using ultrasound (US) to specifically reduce CRT expression in the carotid artery. RESULTS: In vitro, Cre-recombinase-mediated CRT knockdown in isolated, floxed VSMCs decreased the CRT transcript and protein, and attenuated the induction of collagen I protein in response to TGF-beta. TGF-beta stimulation of collagen I was partly blocked by the NFAT inhibitor 11R-VIVIT. Following carotid artery ligation, CRT staining was upregulated with enhanced expression in the neointima 14-21 days after injury. Furthermore, Cre-recombinase-IRES-GFP plasmid delivered by targeted US reduced CRT expression in the neointima of CRT-floxed mice and led to a significant reduction in neointima formation and collagen deposition. The neointimal cell number was also reduced in mice, with a local, tissue-specific knockdown of CRT. CONCLUSIONS: This work establishes a novel role for CRT in mediating VSMC responses to injury through the regulation of collagen deposition and neointima formation. |
