Effects of Salsalate Therapy on Recovery From Vascular Injury in Female Zucker Fatty Rats

Abstract

OBJECTIVESalsalate 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 METHODSSalsalate 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.RESULTSTreatment 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.CONCLUSIONSThe 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.

Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats

“…After one week of stabilization, balloon injury was induced as previously described (Desouza, Murthy, et al, 2003;Murthy, Desouza, et al, 2010;Murthy, St Hilarie, et al, 2010;Murthy et al, 2005). Briefly, the rats were anesthetized with 5% isoflurane in oxygen inhalation and the femoral artery was surgically approached.…”

“…All four segments of the artery (individual) were selected for measurement and analysis at a magnification of × 10. Computerized digital microscopic software (Image-Pro plus 4) was used to obtain measurements of the intimal and medial areas by a previously described method (Desouza, Murthy et al, 2003;Murthy, Desouza, et al, 2010;Murthy, St Hilarie, et al, 2010;Murthy et al, 2005). The I/M ratio was calculated for all specimens for comparison between treatment groups.…”

Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2Akita+/− type-1 diabetic mice

“…Sepiapterin was administered by oral gavage at 0.1 mg per gram of body weight, 13 and salsalate was given at 0.1 g per gram of body weight 14 as an additive mixed in ad libitum diet. The treatments were continued for 16 weeks.…”

“…28,29 On the other hand, dietary supplementation of salsalate had a favorable effect on eNOS/ phospho eNOS expression and upregulation of anti-inflammatory/antioxidant activity in Zucker fatty rats. 14 On the basis of these prior reports and our novel finding that IKKβ blocks eNOS QUOTE activity, 6 a combination of L-arginine, sepiapterin and salsalate diet regimen was formulated and the Ins2…”

Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery

“…The intensity of VEGF protein staining was measured with digitizing software to obtain mean staining density values. [28][29][30] Serum VEGF concentration. Serum levels of VEGF were measured at 3, 7, 14, 21, and 28 days after gene transfection with a commercially available human VEGF Accucyte enzyme-linked immunosorbent assay kit (Millipore, Bedford, Mass), strictly according to the manufacturer's instructions.…”