title: Targeting caveolin-3 for the treatment of diabetic cardiomyopathy.
abstract: Diabetes is a global health problem with more than 550 million people predicted to be diabetic by 2030. A major complication of diabetes is cardiovascular disease, which accounts for over two-thirds of mortality and morbidity in diabetic patients. This increased risk has led to the definition of a diabetic cardiomyopathy phenotype characterised by early left ventricular dysfunction with normal ejection fraction. Here we review the aetiology of diabetic cardiomyopathy and explore the involvement of the protein caveolin-3 (Cav3). Cav3 forms part of a complex mechanism regulating insulin signalling and glucose uptake, processes that are impaired in diabetes. Further, Cav3 is key for stabilisation and trafficking of cardiac ion channels to the plasma membrane and so contributes to the cardiac action potential shape and duration. In addition, Cav3 has direct and indirect interactions with proteins involved in excitation-contraction coupling and so has the potential to influence cardiac contractility. Significantly, both impaired contractility and rhythm disturbances are hallmarks of diabetic cardiomyopathy. We review here how changes to Cav3 expression levels and altered relationships with interacting partners may be contributory factors to several of the pathological features identified in diabetic cardiomyopathy. Finally, the review concludes by considering ways in which levels of Cav3 may be manipulated in order to develop novel therapeutic approaches for treating diabetic cardiomyopathy.
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, M13 9NT, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Murfitt
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, M13 9NT, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Whiteley
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, M13 9NT, UK.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Iqbal
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, M13 9NT, UK. Electronic address: ashraf.kitmitto@manchester.ac.uk.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Kitmitto
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D015316:Genetic Therapy; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D051242:Caveolin 1; D051244:Caveolin 3; D007328:Insulin; D035683:MicroRNAs; D019001:Nitric Oxide Synthase; D005947:Glucose
keywords: Cardiac remodelling; Caveolin-3; Diabetes; Diabetic cardiomyopathy; Excitation–contraction coupling