Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPARα stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.

We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D) and acute myocardial infarction (AMI). Streptozotocin-induced diabetic- (DB-) rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R). Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD), guanosine triphosphate cyclohydrolase I (GTPCH-I) expression, tetrahydrobiopterin : dihydrobiopterin (BH₄ : BH₂) ratio, endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) bioavailability, and decreased inducible NOS (iNOS) activity. These findings suggest that PPARαactivation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D.

Background: Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. Methods: In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. Results: Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P < 0.05 for all). Conclusions: The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. Retrospectively registered: https://clinicaltrials.gov/show/NCT03942822

Background: In animal models of pulmonary arterial hypertension (PAH), angiotensin-converting enzyme (ACE)2 and angiotensin (Ang)-(1–7) have been shown to have vasodilatory, antiproliferative, antifibrotic and antihypertrophic properties. However, the status and role of the ACE2-Ang(1–7) axis in human PAH is incompletely understood.Methods: We studied 85 patients with a diagnosis of PAH of distinct aetiologies. 55 healthy blood donors paired for age and sex served as controls. Blood samples were obtained from the pulmonary artery in patients with PAH during right heart catheterisation. Peripheral blood was obtained for both groups. Ang(1–7) and -II were measured using zone capillary electrophoresis. Aldosterone, Ang(1–9), AngA and ACE2 were measured using ELISA, and ACE2 activity was determined enzymatically.Results: Of the 85 patients, 47 had idiopathic PAH, 25 had PAH associated with congenital heart disease and 13 had PAH associated with collagen vascular disease. Compared to controls, patients with PAH had a higher concentration of AngII (median 1.03, interquartile range 0.72–1.88 pmol·mL⁻¹versus0.19, 0.10–0.37 pmol·mL⁻¹; p<0.001) and of aldosterone (88.7, 58.7–132 ng·dL⁻¹versus12.9, 9.55–19.9 ng·dL⁻¹; p<0.001). Conversely, PAH patients had a lower concentration of Ang(1–7) than controls (0.69, 0.474–0.91 pmol·mL⁻¹versus4.07, 2.82–6.73 pmol·mL⁻¹; p<0.001), and a lower concentration of Ang(1–9) and AngA. Similarly, the ACE2 concentration was higher than in controls (8.7, 5.35–13.2 ng·mL⁻¹versus4.53, 1.47–14.3 ng·mL⁻¹; p=0.011), whereas the ACE2 activity was significantly reduced (1.88, 1.08–2.81 nmol·mL⁻¹versus5.97, 3.1–17.8 nmol·mL⁻¹; p<0.001). No significant differences were found among the three different aetiological forms of PAH.Conclusions: The AngII–ACE2–Ang(1–7) axis appears to be altered in human PAH and we propose that this imbalance, in favour of AngII, plays a role in the pathogenesis of the severe PAH. Further mechanistic studies are warranted.