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Perfluorooctanoic acid-induced exacerbation of myocardial ischemia-reperfusion injury: Roles of peroxisome proliferation activated receptor alpha-related fatty acid metabolism

Year: 2026

Type: article

Abstract: Perfluorooctanoic acid (PFOA) exposure has been associated with various negative effects on the cardiovascular system, including myocardial infarction. During myocardial infarction, ischemia-reperfusion (IR) injury is an important event, significantly affecting prognosis, while the effects of PFOA exposure on IR injury were not previously investigated. In the current study, C57B6 mice were pre-exposed to 0.005, 0.05 or 0.5 mg/kg/day PFOA for four weeks, and then IR injury was achieved with left anterior descending coronary artery ligation. The severity of IR injury was assessed with echocardiography, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin & eosin staining and Masson trichrome staining, along with serum biomarkers for myocardial injury and oxidative stress. To investigate the molecular mechanism, peroxisome proliferation activated receptor alpha (PPAR alpha) antagonist GW6471 was co-administered with PFOA, and animals were subjected to identical morphological, functional and biochemical evaluations. qRT-PCR and western blotting were utilized to assess PPAR alpha downstream genes: carnitine palmitoyl transferase 1b (CPT1b) and fatty acid binding protein 3 (FABP3) in heart tissue samples. The results indicated that pre-exposure to 0.05 or 0.5 mg/kg PFOA for 4 weeks significantly increased the severity of IR injury as indicated by morphological, functional and biochemical parameters, while co-administration of GW6471 alleviated such effects. Pre-exposure to PFOA significantly elevated the expression of CPT1b and FABP3 in myocardial tissues, whose extent corresponded to the severity of IR injury well. Meanwhile, co-exposure to GW6471 effectively alleviated such changes, suggesting that activation of PPAR alpha related fatty acid metabolism is likely involved in PFOA-mediated exacerbation of IR injury.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2026.120602