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


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.
Murthy
Subramanyam N
SN
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Desouza
Cyrus V
CV
Bost
Neal W
NW
Hilaire
Rose-Claire St
RC
Casey
David B
DB
Badejo
Adeleke M
AM
Dhaliwal
Jasdeep S
JS
McGee
Jennifer
J
McNamara
Dennis B
DB
Kadowitz
Philip J
PJ
Fonseca
Vivian A
VA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015153:Blotting, Western; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D005260:Female; D007150:Immunohistochemistry; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D012459:Salicylates / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; C014182:salicylsalicylic acid