Role of COX-2 in vascular inflammation; an experimental model of metabolic syndrome

RENNA NF; LEMBO, C; DIEZ E; MIATELLO RM

MEDIATORS OF INFLAMMATION

HINDAWI PUBLISHING CORPORATION

Lugar: New York; Año: 2013 p. 609 - 619

0962-9351

The objective of this work was to demonstrate the role played by the COX-2 enzyme at the vascular level in vascular remodeling and inflammation, in association with an experimental model of metabolic syndrome arising from the pharmacological administration of lumiracoxib, a COX-2 specific antagonist. Spontaneously hypertensive (SHR) males Wistar Kyoto rats (WKY) were employed; they were distributed in 8 groups (n = 8 each): I-Control (W); II-W+L WKY Receiving 20 mg/kg of lumiracoxib by intraesophageal administration, III-SHR, IV-SHR+L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; V-Fructose-Fed Rats (FFR): WKY Receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; VI-FFR+ L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; VII-Fructose-Fed Hypertensive Rats (FFHR): SHR Receiving 10% (w/v) fructose solution in drinking water during all 12 weeks, and VIII-FFHR+L: FFHR+20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables such as as glucose, triglycerides, cholesterol and blood pressure were evaluated; also morphometric variables such as L/M and relative heart weight; oxidative stress variables and IFI or westerblot immunostained variables of MMP-2 and MMP-9 (collagenases), VCAM-1, and NF-kB. Results and Conclusions: FFHR presented all variables of metabolic syndrome; there was also an increase in NADPH oxidase activity and a decrease of eNOS which contributed to oxidative stress; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.