Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cells to apoptosis during vein arterialization remodeling

Texto completo
Autor(es):
Gastalho Campos, Luciene Cristina [1, 2] ; Ribeiro-Silva, Joao Carlos [1] ; Menegon, Alessandra Santos [1] ; Barauna, Valerio Garrone [3, 1] ; Miyakawa, Ayumi Aurea [1] ; Krieger, Jose Eduardo [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, Sao Paulo - Brazil
[2] Univ Estadual Santa Cruz, Dept Biol Sci, Ilheus, BA - Brazil
[3] Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, ES - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Clinical Science; v. 132, n. 4, p. 449-459, FEB 28 2018.
Citações Web of Science: 0
Resumo

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. (AU)

Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
Beneficiário:José Eduardo Krieger
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 09/50624-5 - Avaliação dos mecanismos regulatórios da crp3/mlp durante a arterialização de enxertos venosos em sistemas ex vivo, in vitro e in vivo
Beneficiário:Luciene Cristina Gastalho Campos
Linha de fomento: Bolsas no Brasil - Pós-Doutorado