title: Statins and oxidative stress in chronic heart failure.
abstract: 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.
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Costa
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Departamento de Medicina Intensiva, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Reina-Couto
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal. Electronic address: albinote@med.up.pt.
authors.forename: António
authors.initials: A
authors.lastname: Albino-Teixeira
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal. Electronic address: tsousa@med.up.pt.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sousa
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species
keywords: Antioxidant/anti‐inflammatory effects; Clinical trials; Efeitos antioxidantes/anti‐inflamatórios; Endothelial nitric oxide synthase; Ensaios clínicos; Estatinas; Heart failure; Insuficiência cardíaca; Nicotinamida adenina dinucleótido fosfato oxidase; Nicotinamide adenine dinucleotide phosphate oxidases; Oxidative stress; Sintetase endotelial de monóxido de azoto; Statins; Stresse oxidativo