Dietary n‐3 fatty acids attenuate cardiac allograft vasculopathy via activating peroxisome proliferator‐activated receptor‐γ

:  Recent in vitro data suggested that n-3 fatty acids could inhibit the activation of PPARγ. This study was designed to test the hypothesis that fish oil ameliorates CAV development via activating PPARγ in an inbred rat model of heart transplantation. Animals were divided into four groups: isograft, control (CsA + vehicle), LFO-treated group (CsA + 0.3% v/w fish oil), and HFO-treated group (CsA + 0.6% v/w fish oil). CsA was administered at 1.5 mg/kg/day for two wk postoperatively. Recipients were treated with fish oil or vehicle daily for eight wk. The histopathological and immunohistochemical examination, activity of NF-κB and PPARγ, intragraft chemokine levels, and chemokine receptor expression were analyzed. Both LFO and HFO significantly decreased the CAV score, inhibited recruitment of T lymphocytes and macrophages, elevated the activity of PPARγ, inhibited the activity of NF-κB, reduced levels of intragraft MCP-1 and IP-10 as well as downregulated expression of chemokine receptors CCR2. CXCR3 expression was not affected. Our results demonstrated that fish oil might attenuate CAV development, possibly through activating PPARγ and subsequently inhibiting the NF-κB activation, the chemokines secretion, as well as the CCR2 expression.