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 language | English (US) |
|---|---|
| Pages (from-to) | 700-709 |
| Number of pages | 10 |
| Journal | Free Radical Biology and Medicine |
| Volume | 50 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2011 |
| Externally published | Yes |
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Keywords
- Catalase
- Ex vivo culture
- Free radicals
- Human saphenous veins
- Protandim
- Scavenging enzymes
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway
AU - Joddar, Binata
AU - Reen, Rashmeet K.
AU - Firstenberg, Michael S.
AU - Varadharaj, Saradhadevi
AU - McCord, Joe M.
AU - Zweier, Jay L.
AU - Gooch, Keith J.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - 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.
AB - 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.
KW - Catalase
KW - Ex vivo culture
KW - Free radicals
KW - Human saphenous veins
KW - Protandim
KW - Scavenging enzymes
UR - http://www.scopus.com/inward/record.url?scp=79951675827&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951675827&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2010.12.008
DO - 10.1016/j.freeradbiomed.2010.12.008
M3 - Article
C2 - 21167278
AN - SCOPUS:79951675827
VL - 50
SP - 700
EP - 709
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 6
ER -