Artery buckling stimulates cell proliferation and NF-κB signaling

Yangming Xiao, Danika Hayman, Seyed Saeid Khalafvand, Merry L Lindsey, Hai Chao Han

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Tortuous carotid arteries are often seen in aged populations and are associated with atherosclerosis, but the underlying mechanisms to explain this preference are unclear. Artery buckling has been suggested as one potential mechanism for the development of tortuous arteries. The objective of this study, accordingly, was to determine the effect of buckling on cell proliferation and associated NF-κB activation in arteries. We developed a technique to generate buckling in porcine carotid arteries using long artery segments in organ culture without changing the pressure, flow rate, and axial stretch ratio. Using this technique, we examined the effect of buckling on arterial wall remodeling in 4-day organ culture under normal and hypertensive pressures. Cell proliferation, NF-κB p65, IκB-α, ERK1/2, and caspase-3 were detected using immunohistochemistry staining and immunoblot analysis. Our results showed that cell proliferation was elevated 5.8-fold in the buckling group under hypertensive pressure (n = 7, P < 0.01) with higher levels of NF-κB nuclear translocation and IκB-α degradation (P < 0.05 for both). Greater numbers of proliferating cells were observed on the inner curve side of the buckled arteries compared with the outer curve side (P < 0.01). NF-κB colocalized with proliferative nuclei. Computational simulations using a fluid-structure interaction model showed reduced wall stress on the inner side of buckled arteries and elevated wall stress on the outer side. We conclude that arterial buckling promotes site-specific wall remodeling with increased cell proliferation and NF-κB activation. These findings shed light on the biomechanical and molecular mechanisms of the pathogenesis of atherosclerosis in tortuous arteries.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number4
DOIs
StatePublished - Aug 15 2014
Externally publishedYes

Fingerprint

Arteries
Cell Proliferation
Organ Culture Techniques
Carotid Arteries
Pressure
Atherosclerosis
Caspase 3
Swine
Cell Count
Immunohistochemistry
Staining and Labeling
Population

Keywords

  • Ex vivo organ culture
  • Mechanical stress
  • Nuclear factor-κB
  • Porcine carotid artery
  • Tortuous arteries
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Artery buckling stimulates cell proliferation and NF-κB signaling. / Xiao, Yangming; Hayman, Danika; Khalafvand, Seyed Saeid; Lindsey, Merry L; Han, Hai Chao.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 307, No. 4, 15.08.2014.

Research output: Contribution to journalArticle

Xiao, Yangming ; Hayman, Danika ; Khalafvand, Seyed Saeid ; Lindsey, Merry L ; Han, Hai Chao. / Artery buckling stimulates cell proliferation and NF-κB signaling. In: American Journal of Physiology - Heart and Circulatory Physiology. 2014 ; Vol. 307, No. 4.
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