Calreticulin Regulates Neointima Formation and Collagen Deposition following Carotid Artery Ligation

Journal of Vascular Research
Kurt A ZimmermanJoanne E Murphy-Ullrich

Abstract

The endoplasmic reticulum (ER) stress protein, calreticulin (CRT), is required for the production of TGF-β-stimulated extracellular matrix (ECM) by fibroblasts. Since TGF-β 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. 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. 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-β. TGF-β 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 c...Continue Reading

Citations

Oct 29, 2017·Journal of Cell Communication and Signaling·Benjamin Y OwusuJoanne E Murphy-Ullrich
Nov 22, 2017·Journal of Cellular and Molecular Medicine·Aristidis S CharonisLuis B Agellon
Nov 11, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Lauren A BiwerBrant E Isakson
May 23, 2019·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Joanne E Murphy-Ullrich
Oct 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Unnati M PandyaLeslie I Gold
Aug 1, 2020·Cell Research·Jitka FucikovaLorenzo Galluzzi

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