Abstract 12891: Loss of Stem Cell Antigen-1 Worsens Vessel Remodeling

Abstract

Background: Stem cell antigen-1 (Sca-1)-expressing progenitor cells contribute to vessel remodeling by differentiating into vascular smooth muscle cells and related myofibroblast-like progeny. However, the functional role for Sca-1 expression in vessel remodeling has not been examined. Here, we assessed the requirement for vascular Sca-1 using a mouse model of Sca-1 deficiency. Methods & Results: Male and female Sca-1-deficient mice (Sca1KO) and C57BL/6N wild-type mice (WT) controls, aged 12-14-wk, were subjected to wire denudation injury of the left common carotid artery. Sca1KO displayed larger neointima at 14d post-injury [35±3mm 2 vs. 25±3mm 2 , p<0.05, n=11-12/group], and more adventitial matrix at 8d [87±3mm 2 vs. 58±4mm 2 , p<0.001, n=9-11/group] and 14d post-injury [109±10mm 2 vs. 51±11mm 2 , p<0.01, n=11-12/group] by Masson’s trichrome staining. Underlying these differences, cell numbers per cross-section were increased in adventitia at 8d [649±27 vs. 435±30, p<0.001, n=9-11/group] and 14d post-injury [778±45 vs. 485±47, p<0.001, n=11-12/group]. Non-leukocyte proliferation by CD45 - Ki67 + staining was increased 1.8-fold in neointima [p<0.01, n=9-11/group] and 1.4-fold in adventitia [p<0.05, n=9-11/group] at 8d post-injury in Sca1KO vs. WT. Cell-type analyses of Sca1KO vs. WT revealed increased pro-fibrotic vimentin + cell proportions at 8d [1.4-fold in neointima, p<0.05; 2.5-fold in media, p<0.001; 1.8-fold in adventitia, p<0.001; n=9-11/group] and 14d post-injury [1.5-fold in neointima, p<0.05; 1.8-fold in media, p<0.05; 1.9-fold in adventitia, p<0.001; n=11-12/group]. CD45 + leukocyte proportions were increased 1.5-fold in neointima [p<0.01, n=9-11/group] and 1.4-fold in adventitia [p<0.01, n=9-11/group] at 8d post-injury, which was also increased 1.5-fold in adventitia by 14d [p<0.01, n=11-12/group]. Conclusion: Taken together, our findings suggest that the loss of Sca-1 worsens remodeling by disinhibiting proliferative, pro-fibrotic, and immune responses to injury, demonstrating a critical role for vascular Sca-1 expression, which may inform novel strategies for the prevention and treatment of vessel remodeling.