Dietary n-3 fatty acids attenuate cardiac allograft vasculopathy via activating peroxisome proliferator-activated receptor-gamma.
Recent in vitro data suggested that n-3 fatty acids could inhibit the activation of PPAR gamma. This study was designed to test the hypothesis that fish oil ameliorates CAV development via activating PPAR gamma 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-kappaB and PPAR gamma, 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 PPAR gamma, inhibited the activity of NF-kappaB, 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 PPAR gamma and subsequently inhibiting the NF-kappaB activation, the chemokines secretion, as well as the CCR2 expression.
Yin
Rong
R
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.
Huang
Hairong
H
Zhang
Junwen
J
Zhu
Jiaquan
J
Jing
Hua
H
Li
Zhongdong
Z
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005395:Fish Oils; D005786:Gene Expression Regulation; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D054390:Receptors, CCR2 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology / Q000628:therapy*
C515334:CCR2 protein, human; D018925:Chemokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D016328:NF-kappa B; D047495:PPAR gamma; D054390:Receptors, CCR2; D019707:Receptors, Chemokine