Table 1.
Summary of studies investigating the role of mitochondria in RIHD.
| References | Tissue type/Study subject | Methods/intervention | Radiation | Result |
|---|---|---|---|---|
| Burch et al. (31) | in vivo; human cardiomyocyte | Electron microscopy of irradiated tissue of mediastinum | 52 Gy, unknown fractionation | Mito swollen; reduced and disorganized cristae; fused double membrane |
| Khan (32) | in vivo; rabbit myocardial cells | Electron microscopy of irradiated heart tissue | 10 or 13 Gy, single dose | Altered mito structure 48 h post-RT exposure |
| Prithivirajsingh et al. (33) | in vitro; human cell lines (dermal fibroblasts, AT, KSS, DNA glioblastoma, and colon carcinoma cell lines) | Evaluation of common deletion | Cesium-137, 4.17 Gy/min, total of 5, 10 or 20 Gy | Increased levels of common deletion 72 h post-RT; dose-independent |
| Azimzadeh et al. (34) | in vivo; C57BL/6 mice; cardiac tissue protein lysates | Proteomic analysis of irradiated mito proteins | TBI, 3 Gy, single dose | 5 and 24 h post-RT—increased levels of proteins involved in oxidative phosphorylation (ATP synthase, NADH dehydrogenase, cytochrome c oxidase) |
| Barjaktarovic et al. (35) | in vivo; C57BL/6N mice; isolated cardiac mito | Mito proteomic and functional analysis of low dose RT localized to heart (4 weeks) | 0.2 or 2 Gy, single dose | 4 weeks post-RT, 2 Gy (functional and proteomic changes); 0.2 Gy functional changes only) |
| Barjaktaroic et al. (36) | in vivo; C57BL/6N mice; isolated cardiac mito | Mito proteomic and functional analysis of late effects (40 weeks) of low dose RT localized to heart | 0.2 or 2 Gy, single dose | 40 weeks post-RT: 2 Gy (functional and proteomic changes); 0.2 Gy (no significant effect) |
| Boerma et al. (37) | in vivo; Gsta4-null vs. WT mice; cardiac tissue | Analysis of cardiac function and proteomics following local heart RT | 18 Gy, single dose | Reduced CO, SV and EF in WT. Increased levels of PGAM5 and Nrf2 in Gsta4-null-mice |
| Azimzadeh et al. (38) | in vivo; C57BL/6 mice; cardiac tissue protein lysates | Analysis of PPAR-α activity following local radiation to the heart | 8 or 16 Gy, single dose | PPAR-α inactivated post-RT with increased FFA, decreased mito complexes I, III, V |
| Azimzadeh et al. (4) | in vivo; human cardiomyocytes | Epidemiologic proteomic analysis following chronic occupational exposures | 100 mcGy−5 Gy, chronic exposure | Dose-dependent increase phosphorylation of PPAR-α and decrease in mito complex I and III and Nrf2 |
| Salata et al. (39) | Wistar rats; left ventricular cardiac tissue | Analysis of apoptotic factors 5 months post-cardiac RT | 20 Gy, single dose | Increased expression Bax/Bcl2, increased apoptotic nuclei |
| Sridharan et al. (40) | Male Sprague-Dawley rats; isolated left ventricular cardiac mito | Analysis of time course of RT mito apoptotic changes (at 2 h−9 months post-RT) | 3–21 Gy, single dose | Bax/Bcl2 ratio elevated (6 h−6 months). Apoptotic nuclei (6 and 24 h and 2 weeks) Increased calcium-induced swelling/ MPT susceptibility (6 h−9 months) |
| Ferreira-Machado et al. (41) | Female Wistar rat cardiomyocytes | Analysis of caspase activity 13 months post heart RT | 15 Gy, single dose | Cleaved/activated caspase at 13 months post-radiation |
| Franco et al. (42) | HEK-293 cells | Analysis of GRK activity post-RT | 4 Gy, single dose | Overexpression of GRK preserved mito morphology, maintained membrane potential and enhanced respiration (3–8 h post-RT) |
RT, Radiation therapy; mito, mitochondria; AT, ataxia telangiectasia; KSS, Kearns Sayre Syndrome; MnSOD, manganese superoxide dismutase; TBI, total body irradiation; WT, wildtype; CO, cardiac output; SV, stroke volume; EF, ejection fraction; FFA, free fatty acids, MPT, membrane permeability transition; RT, radiation therapy.