Fig 1: The age of patients undergoing heart transplantation or LVAD implantation according to the myocardial expression of UPRmt proteins. (a–h) Individual data points represent the age when patients underwent heart transplantation or LVAD implantation (ageHTx/LVAD), and the horizontal line indicates mean values. Patients were divided into two groups according to the myocardial expression of respective UPRmt proteins (CLPP, HSP10, HSP60, mt-HSP70, HTRA2, LONP1, OMA1, SPG7, TOMM20, and YME1L), where half of the patients with a lower expression were assigned to the low group (Lo) group, and half of the patients with a higher expression were assigned to the higher group (Hi). The patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were analyzed separately or together (all). Only significant differences (p < 0.05) are shown.
Fig 2: Effect of UPRmt inhibitors on human cultured cells exposed to oxidative stress. An MTT assay was used to assess viability of cells without any treatment (control, Ctrl), cells treated with antimycin A to induce oxidative stress (AA), and cells treated with combination of AA and one of four different UPRmt inhibitors: (a) EGCG (inhibitor of OMA1); (b) MKT-077 (MKT; inhibitor of mt-HSP70); (c) CDDO (inhibitor of LONP); and (d) nonactin (NA; inhibitor of HSP60). Effects of inhibitors alone, without AA are shown in (e). Data are expressed as means ± SEM with n = 8 for each group. Data are normalized to control (Ctrl). Significant p-values are indicated in graphs.
Fig 3: Protein expression of UPRmt elements and TOMM20 in failing human hearts. (a–j) Protein levels in human myocardial samples were quantified using ELISA kits. Analyses included UPRmt chaperones (HSP10, HSP60, and mt-HSP70), proteases (CLPP, HTRA2, LONP1, OMA1, SPG7, and YME1L), and translocase of the outer mitochondrial membrane TOMM20, which was used to assess mitochondrial content in the myocardium. Summary data are presented as mean value ± SEM. Abbreviations: Ctrl (control; n = 6); DCM (heart failure caused by dilated cardiomyopathy; n = 30); and ICM (heart failure caused by ischemic cardiomyopathy; n = 29). Significant p-values are indicated in graphs.
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