Inflammation has been recognized as a major pathophysiological contributor to the entire spectrum of human heart failure (HF), including HF with reduced ejection fraction, HF with preserved ejection fraction, acute HF and cardiogenic shock. Nevertheless, the results of several trials attempting anti-inflammatory strategies in HF patients have not been consistent or motivating and the clinical implementation of anti-inflammatory treatments for HF still requires larger and longer trials, as well as novel and/or more specific drugs. The present work reviews the different inflammatory mechanisms contributing to each type of HF, the major inflammatory mediators involved, namely tumor necrosis factor alpha, the interleukins 1, 6, 8, 10, 18, and 33, C-reactive protein and the enzymes myeloperoxidase and inducible nitric oxide synthase, and their effects on heart function. Furthermore, several trials targeting these mediators or involving other anti-inflammatory treatments in human HF are also described and analyzed. Future therapeutic advances will likely involve tailored anti-inflammatory treatments according to the patient’s inflammatory profile, as well as the development of resolution pharmacology aimed at stimulating resolution of inflammation pathways in HF.

Statins are the most commonly prescribed drugs for the treatment of dyslipidemia. They are also recommended in primary and secondary prevention of cardiovascular disease. In addition to decreasing cholesterol synthesis, statins interfere with the synthesis of isoprenoid intermediates, which may explain many of their pleiotropic properties, including their antioxidant effects. Oxidative stress is defined as an imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems, with a prevailing pro-oxidant status that results in macromolecular damage and disruption of cellular redox signaling. Reactive oxygen species interfere with various processes that affect cardiac structure and function, contributing to the contractile dysfunction, myocardial hypertrophy and fibrosis observed in the pathophysiology of heart failure. By regulating several molecular pathways that control nicotinamide adenine dinucleotide phosphate oxidase and endothelial nitric oxide synthase activity, statins help restore redox homeostasis. These drugs also contribute to the control of inflammation and appear to have a protective role in various diseases. The results of observational studies and clinical trials with statins in heart failure have not been consensual. This review aims to analyze the role of oxidative stress in heart failure and the molecular mechanisms underlying statins' antioxidant properties. It also examines current scientific evidence on the use of these drugs as a specific treatment for heart failure.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8–9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H₂O₂), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H₂O₂, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H₂O₂ were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H₂O₂ were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P_{for linear trend}=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

BACKGROUND AND PURPOSE Activation of the intrarenal renin‐angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H₂O₂) contribute to hypertension. We examined whether H₂O₂ mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II).EXPERIMENTAL APPROACH Ang II (200 ng·kg⁻¹·min⁻¹) or saline were infused in Sprague Dawley rats from day 0 to day 14. Polyethylene glycol (PEG)‐catalase (10 000 U·kg⁻¹·day⁻¹) was given to Ang II‐treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H₂O₂, angiotensin AT₁ receptor and Nox4 expression and nuclear factor‐κB (NF‐κB) activation were evaluated in the kidney. Plasma and urinary H₂O₂ and angiotensinogen were also measured.KEY RESULTS Ang II increased H₂O₂, AT₁ receptor and Nox4 expression and NF‐κB activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H₂O₂ levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG‐catalase had a short‐term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG‐catalase decreased renal medullary expression of AT₁ receptors and Nox4 in Ang II‐infused rats. Renal medullary NF‐κB activation was correlated with local H₂O₂ levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen.CONCLUSIONS AND IMPLICATIONS The renal medulla is a major target for Ang II‐induced redox dysfunction. H₂O₂ appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H₂O₂ levels may provide future grounds for the treatment of hypertension.