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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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Representative sections of H&E-stained carotid arteries from uninjured (A) and injured and untreated/control (B) Zucker fatty rats. The hyperplastic response that follows injury was significantly reduced when the rats were treated with salsalate (C), and quantitation of the reduction in intimal hyperplasia is depicted in D. Balloon catheter injury results in a hyperplastic response in the injured segment of the artery and salsalate produces a significant attenuation of the response. The reduction in intimal hyperplasia could be attributed, at least in part, to treatment with salsalate. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 1: Representative sections of H&E-stained carotid arteries from uninjured (A) and injured and untreated/control (B) Zucker fatty rats. The hyperplastic response that follows injury was significantly reduced when the rats were treated with salsalate (C), and quantitation of the reduction in intimal hyperplasia is depicted in D. Balloon catheter injury results in a hyperplastic response in the injured segment of the artery and salsalate produces a significant attenuation of the response. The reduction in intimal hyperplasia could be attributed, at least in part, to treatment with salsalate. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: The morphometric measurement of the carotid artery cross-sections from the balloon catheter–injured and untreated or control and salsalate-treated groups of rats had an I/M ratio of 0.9 ± 0.2 vs. 0.19 ± 0.11 (P < 0.05). Representative sections of H&E-stained carotid arteries from uninjured (Fig. 1A), injured, and untreated/control (Fig. 1B) rats are presented in Fig. 1. The treatment with salsalate resulted in significant attenuation of the hyperplastic response. A representative H&E-stained carotid artery section from balloon catheter–injured and salsalate-treated rats is shown in Fig. 1C. The quantitation of intimal hyperplasia is shown in Fig. 1D. These results suggest that the attenuating effect on intimal hyperplasia could be attributed, at least in part, to treatment with salsalate.


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)

Representative sections of H&E-stained carotid arteries from uninjured (A) and injured and untreated/control (B) Zucker fatty rats. The hyperplastic response that follows injury was significantly reduced when the rats were treated with salsalate (C), and quantitation of the reduction in intimal hyperplasia is depicted in D. Balloon catheter injury results in a hyperplastic response in the injured segment of the artery and salsalate produces a significant attenuation of the response. The reduction in intimal hyperplasia could be attributed, at least in part, to treatment with salsalate. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 1: Representative sections of H&E-stained carotid arteries from uninjured (A) and injured and untreated/control (B) Zucker fatty rats. The hyperplastic response that follows injury was significantly reduced when the rats were treated with salsalate (C), and quantitation of the reduction in intimal hyperplasia is depicted in D. Balloon catheter injury results in a hyperplastic response in the injured segment of the artery and salsalate produces a significant attenuation of the response. The reduction in intimal hyperplasia could be attributed, at least in part, to treatment with salsalate. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: The morphometric measurement of the carotid artery cross-sections from the balloon catheter–injured and untreated or control and salsalate-treated groups of rats had an I/M ratio of 0.9 ± 0.2 vs. 0.19 ± 0.11 (P < 0.05). Representative sections of H&E-stained carotid arteries from uninjured (Fig. 1A), injured, and untreated/control (Fig. 1B) rats are presented in Fig. 1. The treatment with salsalate resulted in significant attenuation of the hyperplastic response. A representative H&E-stained carotid artery section from balloon catheter–injured and salsalate-treated rats is shown in Fig. 1C. The quantitation of intimal hyperplasia is shown in Fig. 1D. These results suggest that the attenuating effect on intimal hyperplasia could be attributed, at least in part, to treatment with salsalate.

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