Vascular and systemic effects of rupatadine administration in APOE-knockout mice

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 female mice (Apoe-/-) were fed a Western-type diet, with (Rupatadine) or without (Control) 0.017% w/w rupatadine for 12 weeks. Atherosclerosis development was evaluated in the aorta and at the aortic sinus. A wide panel of organs was evaluated through histological analyses. 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, lymph node and spleen. In Rupatadine lung, a tendency toward an increase in infiltrating mast cells was observed. Atherosclerotic plaque extent in the aorta was comparable between groups. Conversely, in the aortic sinus, plaque area was significantly larger in Rupatadine than in Control. Atherosclerosis worsening in Rupatadine was accompanied by a significantly higher number of CD3+ T lymphocytes both in plaques and in the myocardium immediately surrounding the aortic sinus. Conclusions: We provide the first evidence that Rupatadine treatment in Apoe-/- mice fed Western diet results in a worsening of atherosclerosis development, with plaques characterized by an increased amount of T lymphocytes.