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- W2891051388 abstract "The ER/SR Ca 2+ sensor, Stromal Interaction molecule 1 (STIM1), a key regulator of store-operated calcium entry is expressed in cardiomyocytes and has been implicated in regulating hypertrophic signaling. We have recently shown that mice with a cardiomyocyte-restricted deletion of STIM1 develop dilated cardiomyopathy. Given the importance of Ca 2+ in regulating cardiac metabolism we examined whether a lack of STIM1 alters cardiac metabolism. We found that hearts isolated from 20 week cr STIM1-KO mice exhibit significant changes in cardiac metabolism, observed by a significant reduction in both glucose oxidation (0.75 ± 0.06 v 0.46 ± 0.04 μmol/min/g dry wt, p < 0.01) and net lactate release (15.38 ± 1.29 v 10.23 ± 0.87 μmol/min/g dry wt, p <0.02) in an isolated perfused working heart model in comparison to control mice. These changes occurred independent of any changes in contractile function or oleate oxidation (0.22 ± 0.03 v 0.26 ± 0.02 μmol/min/g dry wt, ns ). Consistent with a reduction in glucose oxidation we also found significant increase in the expression of Pyruvate dehydrogenase kinase and a reduction in the expression of GLUT4 protein levels. Hearts from 20 week cr STIM1-KO contained an increased number of lipid droplets (3.35 ± 0.35 v 2.08 ± 0.20, no of lipid droplets per 4400x grid square, p <0.002) and increased triglyceride levels (51.95 ± 5.84 v 32.55 ± 2.41 v 36.05 ± 1.73 mg/dL, p < 0.05) in comparison to age-matched controls and cr STIM1-KO +/- hearts respectively. In addition to these metabolic changes there were was also significant disruption in mitochondrial morphology and structure in cr STIM1-KO; interesting these same abnormalities were also present in cr STIM1-KO +/- hearts. We found that 12 week cr STIM1-KO +/- and cr STIM1-KO hearts contained smaller mitochondria compared to controls and that cr STIM1-KO were significantly smaller than cr STIM1-KO +/- (1140.6 ± 28.3nm v 973.9 ± 15.8nm v 887.3 ± 17.1nm, p < 0.01) These data demonstrate for the first time a novel yet critical role for STIM1 in regulating cardiac metabolism and in maintaining mitochondrial morphology and organization. This work was supported by NIH grant R21-HL-110366 (JCC) and an American Heart Association Greater Southeast Postdoctoral fellowship 15POST25260004 (HEC)." @default.
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- W2891051388 date "2015-11-10" @default.
- W2891051388 modified "2023-10-15" @default.
- W2891051388 title "Abstract 19844: Stromal Interaction Molecule 1 is Essential for the Maintenance of Cardiac Metabolism" @default.
- W2891051388 doi "https://doi.org/10.1161/circ.132.suppl_3.19844" @default.
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