title: Redox modification of caveolar proteins in the cardiovascular system- role in cellular signalling and disease.
abstract: Rapid and coordinated release of a variety of reactive oxygen species (ROS) such as superoxide (O2.-), hydrogen peroxide (H2O2) and peroxynitrite, in specific microdomains, play a crucial role in cell signalling in the cardiovascular system. These reactions are mediated by reversible and functional modifications of a wide variety of key proteins. Dysregulation of this oxidative signalling occurs in almost all forms of cardiovascular disease (CVD), including at the very early phases. Despite the heavily publicized failure of "antioxidants" to improve CVD progression, pharmacotherapies such as those targeting the renin-angiotensin system, or statins, exert at least part of their large clinical benefit via modulating cellular redox signalling. Over 250 proteins, including receptors, ion channels and pumps, and signalling proteins are found in the caveolae. An increasing proportion of these are being recognized as redox regulated-proteins, that reside in the immediate vicinity of the two major cellular sources of ROS, nicotinamide adenine dinucleotide phosphate oxidase (Nox) and uncoupled endothelial nitric oxide synthase (eNOS). This review focuses on what is known about redox signalling within the caveolae, as well as endogenous protective mechanisms utilized by the cell, and new approaches to targeting dysregulated redox signalling in the caveolae as a therapeutic strategy in CVD.
authors.affiliation: Kolling Institute of Medical Research, University of Sydney and Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Bubb
authors.affiliation: Kolling Institute of Medical Research, University of Sydney and Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Department of Cardiothoracic and Vascular Surgery, Heart and Lung Clinic, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Asa Birna
authors.initials: AB
authors.lastname: Birgisdottir
authors.affiliation: Kolling Institute of Medical Research, University of Sydney and Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: Owen
authors.initials: O
authors.lastname: Tang
authors.affiliation: Kolling Institute of Medical Research, University of Sydney and Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Kolling Institute of Medical Research, University of Sydney and Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Electronic address: gemma.figtree@sydney.edu.au.
authors.forename: Gemma A
authors.initials: GA
authors.lastname: Figtree
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002319:Cardiovascular System / Q000378:metabolism / Q000473:pathology; D021941:Caveolae / Q000378:metabolism* / Q000473:pathology; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D022461:Caveolins; D017382:Reactive Oxygen Species; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases
keywords: Glutaredoxin; Heart failure; Hydrogen peroxide; NADPH oxidase; S-glutathionylation; Superoxide; eNOS