doi: 10.1161/hh1201.092094īisping E, Ikeda S, Kong SW, Tarnavski O, Bodyak N, McMullen JR, Rajagopal S, Son JK, Ma Q, Springer Z, Kang PM, Izumo S, Pu WT (2006) Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Twist basic helix-loop-helix transcription factor 1 VIM:Īkao M, Ohler A, O’Rourke B, Marban E (2001) Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells. Zinc finger E-box-binding homeobox 2 SNAI1: Zinc finger E-box-binding homeobox 1 ZEB2: Sarco/endoplasmic reticulum Ca 2+-ATPase CALM1: Solute carrier family 2 (facilitated glucose transporter), member 4 SERCA 2a: Solute carrier family 2 (facilitated glucose transporter), member 1 SLC2A4: Peroxisome proliferator-activated receptor alpha SLC2A1: Medium-chain acyl-CoA dehydrogenase PPARα: Peroxisome proliferator-activated receptor gamma, co-activator 1 beta CPT1b: Peroxisome proliferator-activated receptor gamma, co-activator 1 alpha PGC1β:
Glutamine fructose-6-phosphate transaminase 2 PGC1α: Glutamine fructose-6-phosphate transaminase 1 GFPT2: Hexosamine biosynthetic pathway O-GlcNAc: We conclude that cardiomyocyte Ogt is not required for cardiomyocyte hypertrophy in vivo however, loss of Ogt may exert subtle phenotypic differences in cardiomyocytes that sensitize the heart to pressure overload-induced ventricular dysfunction. Although no significant differences in cardiac dysfunction were apparent after recombination, it is possible that such changes in dedifferentiation markers could reflect a larger phenotypic shift within the Ogt-deficient cardiomyocytes. Interestingly, markers of cardiomyocyte dedifferentiation were elevated in Ogt-deficient cardiomyocytes. We next determined whether significant differences were present in i-cm Ogt −/− cardiomyocytes from surgically naïve mice. Although some changes in hypertrophic and fibrotic signaling were noted, there were no histological differences in hypertrophy or fibrosis. Deletion of cardiomyocyte Ogt significantly decreased O-GlcNAcylation and exacerbated ventricular dysfunction, without producing widespread changes in metabolic transcripts. To test the role of OGT in the heart, we subjected cardiomyocyte-specific, inducibly deficient Ogt (i-cm Ogt −/−) mice and Ogt competent littermate wild-type (WT) mice to transverse aortic constriction.
Protein O-GlcNAcylation levels were increased in myocardial tissue from heart failure patients compared with normal patients. Here, we addressed this question using patient samples and a preclinical model of heart failure. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues.
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