Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin

心力衰竭和射血分数降低患者的心脏线粒体丙酮酸载体表达减少:缺血性与非缺血性起源

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作者:Paula Lopez-Vazquez, Mariana Fernandez-Caggiano, Eduardo Barge-Caballero, Gonzalo Barge-Caballero, David Couto-Mallon, Zulaika Grille-Cancela, Paula Blanco-Canosa, Maria J Paniagua-Martin, Daniel Enriquez-Vazquez, Jose M Vazquez-Rodriguez, Nieves Domenech, Maria G Crespo-Leiro

Conclusion

Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

Methods

Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.

Results

Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.

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