Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention

Ya Ju Chang, Hui Chun Huang, Yuan Yu Hsueh, Shao Wei Wang, Fong Chin Su, Chih Han Chang, Ming Jer Tang, Yi Shuan Li, Shyh Hau Wang, Kirk K. Shung, Shu Chien, Chia Ching Wu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.

Original languageEnglish
Article number22147
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Feb 26

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Neointima
Autophagy
Veins
Transplants
Ultrasonics
Endothelial Cells
Mechanical Stress
Endothelium
Hyperplasia
Pathologic Constriction
Perfusion
Apoptosis
3-methyladenine

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention",
abstract = "Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.",
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Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation : Prediction and Prevention. / Chang, Ya Ju; Huang, Hui Chun; Hsueh, Yuan Yu; Wang, Shao Wei; Su, Fong Chin; Chang, Chih Han; Tang, Ming Jer; Li, Yi Shuan; Wang, Shyh Hau; Shung, Kirk K.; Chien, Shu; Wu, Chia Ching.

In: Scientific reports, Vol. 6, 22147, 26.02.2016.

Research output: Contribution to journalArticle

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AU - Su, Fong Chin

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AU - Tang, Ming Jer

AU - Li, Yi Shuan

AU - Wang, Shyh Hau

AU - Shung, Kirk K.

AU - Chien, Shu

AU - Wu, Chia Ching

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