title: Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.
abstract: NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania.
authors.forename: Simona-Adriana
authors.initials: SA
authors.lastname: Manea
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Constantin
authors.affiliation: "Victor Babes" National Institute of Pathology, Bucharest, Romania.
authors.forename: Gina
authors.initials: G
authors.lastname: Manda
authors.affiliation: The Institute for Drug Research, Department of Pharmacology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Sasson
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania. Electronic address: adrian.manea@icbp.ro.
authors.forename: Adrian
authors.initials: A
authors.lastname: Manea
mesh_terms: D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019255:NADPH Oxidases
keywords: Cardiovascular diseases; Epigenetics; NADPH oxidase; Transcription factors