Open AccessSmooth muscle cell‐specific Tgfbr1 deficiency attenuates neointimal hyperplasia but promotes an undesired vascular phenotype for injured arteries
Author(s) -
Liao Mingmei,
Yang Pu,
Wang Fen,
Berceli Scott A.,
Ali Yasmin H.,
Chan Kelvin L.,
Jiang Zhihua
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13056
Subject(s) - neointimal hyperplasia , vascular smooth muscle , phenotype , medicine , hyperplasia , cell , cancer research , cardiology , endocrinology , smooth muscle , chemistry , restenosis , stent , gene , biochemistry
Abstract Neointimal hyperplasia ( NIH ) and inward wall remodeling cause arterial restenosis and failure of bypass vein grafts. Previous studies from our group suggest that transforming growth factor ( TGF ) β promotes these pathologies via regulating cell kinetics at the early stage and matrix metabolism at the late stage. Although these temporal TGF β effects may result from its signaling in different cell groups, the responsible cell type has not been identified. In the current study, we evaluated the effect of smooth muscle cell ( SMC )‐specific TGF β signaling through its type I receptor TGFBR 1 on NIH and wall remodeling of the injured femoral arteries ( FA s). An inducible Cre/loxP system was employed to delete SMC Tgfbr1 ( Tgfbr1 iko ). Mice not carrying the Cre allele ( Tgfbr1 f/f ) served as controls. The injured FA s were evaluated on d3, d7, and d28 postoperatively. Tgfbr1 iko attenuated NIH by 92%, but had insignificant influence on arterial caliber when compared with Tgfbr1 f/f controls on d28. This attenuation correlated with greater cellularity and reduced collagen content. Compared with Tgfbr1 f/f FA s, however, Tgfbr1 iko FA s exhibited persistent neointimal cell proliferation and cell apoptosis, with both events at a greater rate on d28. Tgfbr1 iko FA s additionally contained fewer SMC s and more inflammatory infiltrates in the neointima and displayed a thicker adventitia than did Tgfbr1 f/f FA s. More MMP 9 proteins were detected in the adventitia of Tgfbr1 iko FA s than in that of Tgfbr1 f/f controls. Our results suggest that disruption of SMC Tgfbr1 inhibits arterial NIH in the short term, but the overall vascular phenotype may not favor long‐term performance of the injured arteries.