Effects of a COX-2 antagonist on vascular inflammation

NICOLÁS RENNA; MARCELA VÁZQUEZ; CRISTINA LAMA; SUSANA GONZALEZ; ROBERTO MIATELLO

Buenos Aires. Argentina

Congreso; XVIth Wold Congress of Cardiology; 2008

World Heart Federetion. Sociedad Argentina de CArdiología. Federacion Argentina de Cardiología

EFFECTS OF A COX-2 ANTAGANONIST ON VASCULAR INFLAMMATION ASSOCIATED TO A MODEL OF METABOLIC SYNDROME Renna NF, Gonzalez ES, Lama MC and Miatello RM. Dept. of Pathology - School of Medicine. U.N.Cuyo. Mendoza, Argentina. Laboratory of Cardiovascular Pathophysiology. IMBECU-CONICET. Argentina. Introduction: Inflammation appears to have a major role in development of vascular remodelling and atherosclerosis. Ciclooxigenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, could be implicated in the expression of matrix metalloproteinases (MMP). Objective: to examine the effect of COX-2 inhibitions and its relationship with vascular remodelling through the administration of lumiracoxib (L), a COX-2 antagonist, in a metabolic syndrome experimental model (MS). Methods:  Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls were distributed in 4 groups (n=16 each). 10% fructose solution was administrated along 12 weeks (FFHR and FFR respectively). For the last 6 weeks groups were divided (n=8 each) and received 20 mg/kg lumiracoxib (L) by gavage. The data (media±sem) were processed by ANOVA and Bonferroni post-test. Symbol * indicates p<0.01 v WKY and # p<0.01 v FFHR. Results: FFHR developed MS compared to their control WKY: increased systolic blood pressure (SBP-mmHg): 182±1 v 118±0.05 *; basal glycemia (BG-mg/dL) 140±5 v 86±5*; HOMA index 2.3±0.0 v 0.4±0.0*; plasma triglyceride (TG-mg/dL) 120±30 v 50±2*; and decreased HDL-col (HL-mg/dL) 10±3 v 18±2*. Moreover, FFHR developed cardiac hypertrophy: increased relative heart weight (RHW) 4.1±0.02 v 2.5±0.01*, left ventricular myocardiocyte cross-sectional area (MCA-ì2): 1550±29 v 800±20*. The coronary artery lumen/media (L/M) ratio decreased: 11±0.5 v 14±1* and the expression of MMP-2 and MMP-9 by western blot in left ventricular homogenates was incremented in FFHR. Vascular inflammation was demonstrated immunohistochemically (IHC) by determination of NF-kB and VCAM-1 in coronary arteries, and high-sensitive Reactive C protein (hsRCP) in plasma: 1.5±0.1 v 5.1±0.2*. Most of these changes were reverted by chronic administration of L: SBP reduced to 165±0.9#   and the coronary artery lumen/media (L/M) ratio was reverted. Cardiac remodelling was also prevented: RHW decreased to 3.5±0.01# and MCA:  1050±29#. The MMP-2 and MMP-9 expression decrease by lumiracoxib administration. Vascular inflammation markers were also reduced: hsRCP: 2.5±0.1# and local expression of NF-kB and VCAM-1 disappeared. Conclusion: These data confirm the development of the pathological experimental model and suggest that consequent activation of genes participating in the inflammatory process takes actively part in the end organ damage at vascular level in this pathology. Additionally, this study demonstrates that the COX-2 antagonist was able to prevent the structural and inflammatory changes associated to the MS experimental model, suggesting the participation of this enzyme in the development of the changes above mentioned.