Vein graft failure limits the long-term patency of the saphenous vein used as a conduit for coronary artery bypass graft. Early graft adaptation involves some degree of intima hyperplasia to sustain the hemodynamic stress, but the progress to occlusion in some veins remains unclear. We have demonstrated that stretch-induced up-regulation of cysteine and glycine-rich protein 3 (Crp3) in rat jugular vein and human saphenous vein in response to arterialization. Here, we developed a Crp3-knockout (KO) rat to investigate the role of Crp3 in vascular remodeling. After 28 days of jugular vein arterialization, the intima layer was three-fold thicker in the Crp3-KO that showed comparable smooth muscle cells (SMC) proliferation but an absence of early apoptosis observed in the wild-type (WT) rat. We then investigated the role of Crp3 in early integrin-mediated signaling apoptosis in isolated jugular SMC. Interestingly, under basal conditions, ceramide treatment failed to induce apoptosis in both WT and Crp3-KO SMC. Under stretch, Crp3 expression increased in WT SMC and ceramide-induced apoptosis. Immunoblotting analysis indicated that ceramide stretch-induced apoptosis in SMC is accompanied by a decrease in the phosphorylation status of both focal adhesion kinase (Fak) and protein kinase B (Akt), leading to an increase in Bax expression and caspase-3 cleavage. In contrast, ceramide failed to decrease Fak and Akt phosphorylation in Crp3-KO SMC and, therefore, there was no downstream induction of Bax expression and effector caspase-3 cleavage. Taken together, we provide evidence that stretch-induced Crp3 modulates vein remodeling in response to arterialization by sensitizing SMC to apoptosis.
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A representative image of an airway from a mouse sensitized and challenged with an allergen. The histological image was captured 24 hours after allergen exposure at which point airway hyperresponsiveness persists without any discernible change to wall structure. In Clinical Science volume 132, issue 3, Wang et al. report on the effects of airway remodelling and allergy on airway responsiveness; for details see pages 327–338. Image kindly provided by Kimberley C.W. Wang (The University of Western Australia).
Research Article|
February 22 2018
Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cells to apoptosis during vein arterialization remodeling
Luciene Cristina Gastalho Campos;
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
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João Carlos Ribeiro-Silva;
João Carlos Ribeiro-Silva
*
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
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Alessandra Santos Menegon;
Alessandra Santos Menegon
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
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Valerio Garrone Barauna;
Valerio Garrone Barauna
‡
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
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Ayumi Aurea Miyakawa;
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Correspondence: Ayumi Aurea Miyakawa ([email protected]) or Jose Eduardo Krieger ([email protected])
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Jose Eduardo Krieger
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Correspondence: Ayumi Aurea Miyakawa ([email protected]) or Jose Eduardo Krieger ([email protected])
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Publisher: Portland Press Ltd
Received:
December 06 2017
Revision Received:
January 26 2018
Accepted:
January 31 2018
Accepted Manuscript online:
February 02 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (4): 449–459.
Article history
Received:
December 06 2017
Revision Received:
January 26 2018
Accepted:
January 31 2018
Accepted Manuscript online:
February 02 2018
Citation
Luciene Cristina Gastalho Campos, João Carlos Ribeiro-Silva, Alessandra Santos Menegon, Valerio Garrone Barauna, Ayumi Aurea Miyakawa, Jose Eduardo Krieger; Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cells to apoptosis during vein arterialization remodeling. Clin Sci (Lond) 28 February 2018; 132 (4): 449–459. doi: https://doi.org/10.1042/CS20171601
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