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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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The RDUs obtained from the densitometric scan of the Western blots for the expression of phosphorylated eNOS (ser 1177) (after normalizing expression levels to corresponding β-actin) in aortic tissue showed an upregulation of p-eNOS by salsalate therapy. There was a significant difference in the mean RDU between the control and salsalate-treated rats (0.2 ± 0.06 vs. 2.0 ± 0.5; P < 0.005). Compared with the control rats, the expression of p-eNOS was increased 10-fold (2.0/0.2). The ratio of the expression of p-eNOS to eNOS in the control animals was 6:1 (0.2/0.03) and in the salsalate-treated rats was 13:1 (2.0/0.15).
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Figure 4: The RDUs obtained from the densitometric scan of the Western blots for the expression of phosphorylated eNOS (ser 1177) (after normalizing expression levels to corresponding β-actin) in aortic tissue showed an upregulation of p-eNOS by salsalate therapy. There was a significant difference in the mean RDU between the control and salsalate-treated rats (0.2 ± 0.06 vs. 2.0 ± 0.5; P < 0.005). Compared with the control rats, the expression of p-eNOS was increased 10-fold (2.0/0.2). The ratio of the expression of p-eNOS to eNOS in the control animals was 6:1 (0.2/0.03) and in the salsalate-treated rats was 13:1 (2.0/0.15).

Mentions: The relative density units (RDUs) obtained from the densitometric scan of the Western blots (after normalizing expression levels to corresponding β-actin) indicate a significant increase in the expression of eNOS in aortic arch protein samples from salsalate-treated rats (0.15 ± 0.07) as compared with the control group (0.03 ± 0.01) (P < 0.05), indicating a fivefold increase (0.15/0.03) (Fig. 3). The p-eNOS expression was increased in aortic arch samples from salsalate-treated rats (2.0 ± 0.5) compared with expression in control rats (0.2 ± 0.06) (P < 0.005), indicating a 10-fold increase (2.0/0.2). The ratio of p-eNOS to eNOS in the control animals was 6-to-1 (0.2/0.03) and 13-to-1 (2.0/0.15) in the rats treated with salsalate (Fig. 4). These results indicate that there was a significant increase in the level of p-eNOS in salsalate-treated rats.


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 RDUs obtained from the densitometric scan of the Western blots for the expression of phosphorylated eNOS (ser 1177) (after normalizing expression levels to corresponding β-actin) in aortic tissue showed an upregulation of p-eNOS by salsalate therapy. There was a significant difference in the mean RDU between the control and salsalate-treated rats (0.2 ± 0.06 vs. 2.0 ± 0.5; P < 0.005). Compared with the control rats, the expression of p-eNOS was increased 10-fold (2.0/0.2). The ratio of the expression of p-eNOS to eNOS in the control animals was 6:1 (0.2/0.03) and in the salsalate-treated rats was 13:1 (2.0/0.15).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: The RDUs obtained from the densitometric scan of the Western blots for the expression of phosphorylated eNOS (ser 1177) (after normalizing expression levels to corresponding β-actin) in aortic tissue showed an upregulation of p-eNOS by salsalate therapy. There was a significant difference in the mean RDU between the control and salsalate-treated rats (0.2 ± 0.06 vs. 2.0 ± 0.5; P < 0.005). Compared with the control rats, the expression of p-eNOS was increased 10-fold (2.0/0.2). The ratio of the expression of p-eNOS to eNOS in the control animals was 6:1 (0.2/0.03) and in the salsalate-treated rats was 13:1 (2.0/0.15).
Mentions: The relative density units (RDUs) obtained from the densitometric scan of the Western blots (after normalizing expression levels to corresponding β-actin) indicate a significant increase in the expression of eNOS in aortic arch protein samples from salsalate-treated rats (0.15 ± 0.07) as compared with the control group (0.03 ± 0.01) (P < 0.05), indicating a fivefold increase (0.15/0.03) (Fig. 3). The p-eNOS expression was increased in aortic arch samples from salsalate-treated rats (2.0 ± 0.5) compared with expression in control rats (0.2 ± 0.06) (P < 0.005), indicating a 10-fold increase (2.0/0.2). The ratio of p-eNOS to eNOS in the control animals was 6-to-1 (0.2/0.03) and 13-to-1 (2.0/0.15) in the rats treated with salsalate (Fig. 4). These results indicate that there was a significant increase in the level of p-eNOS in salsalate-treated rats.

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