Role of Protein Disulfide Isomerase during vascular repair after injury
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conferenceObject
Data de publicação
2012
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Editora
FEDERATION AMER SOC EXP BIOL
Citação
FASEB JOURNAL, v.26, 2012
Resumo
Endoplasmic reticulum(ER) redox chaperone protein disulfide isomerase(PDI) regulates vascular/phagocytic NADPH oxidase and supports cell migration. We investigated the role of PDI during vascular repair after injury(AI) induced by balloon in rabbit iliac artery. There was marked increase of PDI mRNA and protein(5–10-fold) at 4, 7 and 14 days AI vs. intact control(CT). PDI immunostaining was greater in intima = neo-endothelium > media. Increased cell-surface PDI was also evident. ER stress-related KDEL chaperones also increased with similar time-course AI. PDI siRNA(siPDI) transfection in cultured vessel rings collected 14 days AI enhanced KDEL expression vs. scrambled siRNA(siScr) (siScr 2.1±0.9 vs. siPDI 5.0±2.3-fold vs. CT, p<0.05), apoptosis (siScr 4.6±0.2 vs. siPDI 6.2±0.9 %TUNEL + nuclei, p<0.05) and proliferation marker PCNA (siScr 1.2±0.3 vs. siPDI 4.0 ±0.2 AU, p<0.05), and decreased differentiation marker calponin-C (siScr 0.52±0.04 vs. siPDI 0.36 ±0.04 AU, p<0.05). siPDI in CT rings did not alter such variables. PCR array analysis showed analogous pattern of mRNA changes. Also, siPDI 14 days AI upregulated Nox1 and downregulated Nox4 NADPH oxidase, while siPDI attenuated oxidant production (in situ hydroethidine) only in CT vessels. Thus, strongly-overexpressed PDI 14 days AI protects against apoptosis and ER stress and sustains VSMC differentiation.