171 - Chronic rupatadine treatment worsens atherosclerosis progression in apolipoprotein E knockout mice fed Western-type diet (ID 1346)
Abstract
Background and Aims
Rupatadine is an N-alkyl pyridine derivative exerting anti-inflammatory properties through the inhibition of a range of mediators. Its primary mechanism of action is through the histamine H1 receptor, with an additional antagonist activity towards PAF. The potent anti-inflammatory effects displayed by rupatadine could be exploited against atherosclerosis development.
Methods
Apolipoprotein E-deficient (EKO) mice (n=15 per group) were fed Western-type diet, with (Rupa) or without (Ctrl) 0.17 g/kg rupatadine for 12 weeks (~16 mg/kg/die).
Results
Weight gain, food/water intake, organ weights were similar in both groups. Plasma total cholesterol and triglyceride levels were also comparable. No difference in inflammatory infiltrates was detected in liver, kidney and lungs. Atherosclerotic plaque extent in arch, thoracic and abdominal segments of aorta (en-face) was comparable between groups. Ctrl and Rupa plaques were remarkably similar in the macrophage content (anti-Galectin3), necrotic core and plaque matrix content (Masson’s trichrome). However, plaque area at the aortic sinus (H&E) was higher in Rupa (+14.8%, p=0.02, Fig.1A, Fig.1B).
Conclusions
Rupatadine treatment in apoE-KO mice fed Western diet resulted in a moderate worsening of atherosclerosis development. Shedding light on controversial in vitro results, our findings are in line with evidences from other related molecules (cetirizine, fexofenadine). While the molecular mechanism is still under investigation, it would be worthwhile to assess the impact of rupatadine treatment on human health, especially in chronically treated patients.
