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Effects of salsalate therapy on recovery from vascular injury in female Zucker fatty rats.

Murthy SN, Desouza CV, Bost NW, Hilaire RC, Casey DB, Badejo AM, Dhaliwal JS, McGee J, McNamara DB, Kadowitz PJ, Fonseca VA - Diabetes (2010)

Bottom Line: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats.The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels.These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.

ABSTRACT

Objective: Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury.

Research design and methods: Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied.

Results: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats.

Conclusions: The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.

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Related in: MedlinePlus

The Western blot analysis of aortic arch NF-κB subunit p65 indicated a significant decrease expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.1599 ± 0.1092 vs. 0.6003 ± 0.11; P = 0.01). The data indicates that salsalate treatment reduced the inflammatory response following the balloon catheter injury of the carotid artery.
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Figure 5: The Western blot analysis of aortic arch NF-κB subunit p65 indicated a significant decrease expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.1599 ± 0.1092 vs. 0.6003 ± 0.11; P = 0.01). The data indicates that salsalate treatment reduced the inflammatory response following the balloon catheter injury of the carotid artery.

Mentions: The results of Western blot analysis of the aortic arch for NFκB subunit p65 showed a significant decrease in expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.159 ± 0.054 vs. 0.600 ± 0.110; P < 0.05). This decrease indicates that downregulation of the NFκB p65 pathway may have a role in the beneficial effect of salsalate in attenuating the inflammatory response following carotid artery balloon catheter injury (Fig. 5).


Effects of salsalate therapy on recovery from vascular injury in female Zucker fatty rats.

Murthy SN, Desouza CV, Bost NW, Hilaire RC, Casey DB, Badejo AM, Dhaliwal JS, McGee J, McNamara DB, Kadowitz PJ, Fonseca VA - Diabetes (2010)

The Western blot analysis of aortic arch NF-κB subunit p65 indicated a significant decrease expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.1599 ± 0.1092 vs. 0.6003 ± 0.11; P = 0.01). The data indicates that salsalate treatment reduced the inflammatory response following the balloon catheter injury of the carotid artery.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992788&req=5

Figure 5: The Western blot analysis of aortic arch NF-κB subunit p65 indicated a significant decrease expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.1599 ± 0.1092 vs. 0.6003 ± 0.11; P = 0.01). The data indicates that salsalate treatment reduced the inflammatory response following the balloon catheter injury of the carotid artery.
Mentions: The results of Western blot analysis of the aortic arch for NFκB subunit p65 showed a significant decrease in expression in the salsalate-treated group (mean relative densities of the salsalate-treated and control groups: 0.159 ± 0.054 vs. 0.600 ± 0.110; P < 0.05). This decrease indicates that downregulation of the NFκB p65 pathway may have a role in the beneficial effect of salsalate in attenuating the inflammatory response following carotid artery balloon catheter injury (Fig. 5).

Bottom Line: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats.The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels.These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.

ABSTRACT

Objective: Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury.

Research design and methods: Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied.

Results: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats.

Conclusions: The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.

Show MeSH
Related in: MedlinePlus