title: FoxO1 is crucial for sustaining cardiomyocyte metabolism and cell survival.
abstract: Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentially switching on protein targets like FoxOs, initiators of cell death. FoxO1, a prominent member of the forkhead box family and subfamily O of transcription factors and produced from the FKHR gene, is involved in regulating metabolism, cell proliferation, oxidative stress response, immune homeostasis, pluripotency in embryonic stem cells, and cell death. In this review we describe distinctive functions of FoxOs, specifically FoxO1 under conditions of nutrient excess, insulin resistance and diabetes, and its manipulation to restore metabolic equilibrium to limit cardiac damage due to cell death. Because FoxO1 helps cardiac tissue to combat a variety of stress stimuli, it could be a major determinant in regulating diabetic cardiomyopathy. In this regard, we highlight studies from our group and others who illustrate how cardiac tissue-specific FoxO1 deletion protects the heart against cardiomyopathy and how its down-regulation in endothelial tissue could prevent against atherosclerotic plaques. In addition, we also describe studies that show FoxO1's beneficial qualities by highlighting their role in inducing anti-oxidant, autophagic, and anti-apoptotic genes under stress conditions of ischaemia-reperfusion and myocardial infarction. Thus, the aforementioned FoxO1 traits could be useful in curbing cardiac tissue-specific impairment of function following diabetes.
authors.affiliation: Faculty of Pharmaceutical Sciences,  The University of British Columbia, 2146 East Mall, Vancouver, BC,  Canada V6T 1Z3.
authors.forename: Prasanth
authors.initials: P
authors.lastname: Puthanveetil
authors.forename: Andrea
authors.initials: A
authors.lastname: Wan
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D058065:Diabetic Cardiomyopathies / Q000503:physiopathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors