Table 2
Characteristics of Loss-of-Function Models for PGC-1 Proteins in Response to Pressure Overload
| Knockout Models | PGC-1α-KO | PGC-1β-KO |
|---|---|---|
| Parameter | ||
| Heart size | ↑ | = |
| Fibrosis | = / ↑ | ↑ |
| Contractile performance and capacity | ||
| Echocardiography | ↓ | ↓ |
| LV Cath | ↓ | ↓ |
| Cardiac output (IWH) | ND | = (3 wk post TAC) |
| Cardiac power (IWH) | ND | = (3 wk post TAC) |
| Mitochondrial volume density | ND | = |
| Mitochondrial function / Energetic reserves | ||
| VADP | ND | = Pyr, ↓ PC |
| ATP-synthesis | ND | = Pyr, ↓ PC |
| ATP/O | ND | = Pyr, = PC |
| ↓ succinate dehydrogenase / cytochrome oxidase (in situ activity stains) | ||
| ↓ Citrate synthase | ||
| Substrate metabolism | ||
| Glucose oxidation | ND | ↓ (3 wk post TAC) |
| Glycolysis | ND | ↓ (3 wk post TAC) |
| Palmitate oxidation | ND | = (3 wk post TAC) |
| FAO gene expression | = / ↓ | = |
| OXPHOS gene expression | = / ↓ | = / ↓ |
| ANP, BNP expression | ↑ | = |
| Oxidative stress | ↑ | ↑ |
| References | Arany et al. 2006; Lu et al. 2010 | Riehle et al. 2011 |
ND, not determined. FAO, fatty acid oxidation; IWH, isolated working heart preparations; LV Cath, left ventricular catheterization; OXPHOS, oxidative phosphorylation; VADP, maximal mitochondrial oxygen consumption following incubation of saponin permeabilized cardiac fibers to ADP with pyruvate (Pyr) or palmitoyl-L-carnitine (PC) as substrate respectively, each combined with malate. Characteristics for PGC-1β-KO mice are presented vs. TAC operated WT controls 8 weeks post TAC unless otherwise indicated. No gain-of-function models for PGC-1 proteins in response to pressure overload have been described yet. No transgenic mouse model with modulated PRC expression in the heart has been yet reported.