No abstract

Peroxisome Proliferator‐Activated Receptor alpha (PPARα) is known to exert many cardiorenal protective effects. In contrast, T‐ helper 17 (Th17) and CD36 have been implicated in hypertension (HTN) and Inflammation. PPARα has been found to promote CD36 function. We hypothesized that PPARα exerts anti‐inflammatory effect by inhibiting CD36‐induced Th17 activation in the kidney in Angiotensin II (AngII)–induced renal injury. The aim of this study is to evaluate the role of PPARα in amelioration of hypertensive renal injury due to CD36‐mediated Th17 activation in HTN. In animals treated with WY14643, a PPARα agonist, or GW6471, a PPARα antagonist, no significant difference in blood pressure (BP) was found between control and Ang II animals. However, GW6471 increased BP (188 ± 23 Vs154 ± 9 mmHg; P<0.01). Ang II increased proteinuria (P<0.001). WY14643 decreased proteinuria caused by Ang II at 14 days (36 ± 5 Vs 64 ± 19 mg/day; P<0.05), while GW6471 was without effect. Ang II did not affect PPARα or CD36 protein expression and WY14643 and GW6471 were also without effect. However, urine IL‐17 was higher in animals treated with Ang II and GW6471 (P<0.05). On the other hand, WY14643 caused a reduction in urine IL‐17 (P<0.01). We conclude that PPARα has renoprotective and anti‐inflammatory effects through inhibition of Th17 but not CD36. This mechanism may be important in the treatment of renal injury after Ang II treatment.