Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway

Binata Joddar, Rashmeet K. Reen, Michael S. Firstenberg, Saradhadevi Varadharaj, Joe M. McCord, Jay L. Zweier, Keith J. Gooch

Research output: Contribution to journalArticle

Abstract

Human saphenous veins (HSVs) are widely used for bypass grafts despite their relatively low long-term patency. To evaluate the role of reactive oxygen species (ROS) signaling in intima hyperplasia (IH), an early stage pathology of vein-graft disease, and to explore the potential therapeutic effects of up-regulating endogenous antioxidant enzymes, we studied segments of HSV cultured ex vivo in an established ex vivo model of HSV IH. Results showed that HSV cultured ex vivo exhibit an ∼3-fold increase in proliferation and ∼ 3.6-fold increase in intimal area relative to freshly isolated HSV. Treatment of HSV during culture with Protandim, a nutritional supplement known to activate Nrf2 and increase the expression of antioxidant enzymes in several in vitro and in vivo models, blocks IH and reduces cellular proliferation to that of freshly isolated HSV. Protandim treatment increased the activity of SOD, HO-1, and catalase 3-, 7-, and 12-fold, respectively, and decreased the levels of superoxide (O2•-) and the lipid peroxidation product 4-HNE. Blocking catalase activity by cotreating with 3-amino-1,2,4-triazole abrogated the protective effect of Protandim on IH and proliferation. In conclusion, these results suggest that ROS-sensitive signaling mediates the observed IH in cultured HSV and that up-regulation of endogenous antioxidant enzymes can have a protective effect.

Original languageEnglish (US)
Pages (from-to)700-709
Number of pages10
JournalFree Radical Biology and Medicine
Volume50
Issue number6
DOIs
StatePublished - Mar 15 2011
Externally publishedYes

Fingerprint

Tunica Intima
Saphenous Vein
Catalase
Hyperplasia
Antioxidants
Grafts
Reactive Oxygen Species
Enzymes
Amitrole
Pathology
Superoxides
Lipids
Transplants
Protandim
Therapeutic Uses
Lipid Peroxidation
Veins
Up-Regulation
Cell Proliferation

Keywords

  • Catalase
  • Ex vivo culture
  • Free radicals
  • Human saphenous veins
  • Protandim
  • Scavenging enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Joddar, B., Reen, R. K., Firstenberg, M. S., Varadharaj, S., McCord, J. M., Zweier, J. L., & Gooch, K. J. (2011). Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway. Free Radical Biology and Medicine, 50(6), 700-709. https://doi.org/10.1016/j.freeradbiomed.2010.12.008

Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway. / Joddar, Binata; Reen, Rashmeet K.; Firstenberg, Michael S.; Varadharaj, Saradhadevi; McCord, Joe M.; Zweier, Jay L.; Gooch, Keith J.

In: Free Radical Biology and Medicine, Vol. 50, No. 6, 15.03.2011, p. 700-709.

Research output: Contribution to journalArticle

Joddar, Binata ; Reen, Rashmeet K. ; Firstenberg, Michael S. ; Varadharaj, Saradhadevi ; McCord, Joe M. ; Zweier, Jay L. ; Gooch, Keith J. / Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway. In: Free Radical Biology and Medicine. 2011 ; Vol. 50, No. 6. pp. 700-709.
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