Stimulus specific changes of energy metabolism in hypertrophied heart.
Cardiac energy metabolism is a determinant of the response to hypertrophic stimuli. To investigate how it responds to physiological or pathological stimuli, we compared the energetic status in models of hypertrophy induced by physiological stimuli (pregnancy or treadmill running) and by pathological stimulus (spontaneously hypertensive rats, SHR) in 15 week-old female rats, leading to a 10% cardiac hypertrophy. Late stage of compensated hypertrophy was also studied in 25 week-old SHR (35% of hypertrophy). Markers of cardiac remodelling did not follow a unique pattern of expression: in trained rats, only ANF was increased; in gravid rats, calcineurin activation and BNP expression were reduced while beta-MHC expression was enhanced; all markers were clearly up-regulated in 25 week-old SHR. Respiration of permeabilized fibers revealed a 17% increase in oxidative capacity in trained rats only. Mitochondrial enzyme activities, expression of the master regulator PGC-1alpha and mitochondrial transcription factor A, and content of mitochondrial DNA were not consistently changed, suggesting that compensated hypertrophy does not involve alterations of mitochondrial biogenesis. Mitochondrial fatty acid utilization tended to increase in trained rats and decreased by 14% in 15 week-old SHR. Expression of markers of lipid oxidation, PPARalpha and its down-stream targets MCAD and CPTI, was up-regulated after training and tended to decrease in gravid and 15 week-old SHR rats. Taken together these results show that there is no univocal pattern of cardiac adaptation in response to physiological or pathological hypertrophic stimuli, suggesting that other factors could play a role in determining adaptation of energy metabolism to increased workload.
Rimbaud
S
S
INSERM, U-769, Châtenay-Malabry, France.
Sanchez
H
H
Garnier
A
A
Fortin
D
D
Bigard
X
X
Veksler
V
V
Ventura-Clapier
R
R
D042964:Acyl-CoA Dehydrogenase / Q000235:genetics; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D047493:PPAR alpha / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats
D051275:Glucose Transporter Type 4; D047908:Intracellular Signaling Peptides and Proteins; C000594638:MYH7 protein, rat; D047493:PPAR alpha; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C495694:Slc2a4 protein, rat; C472610:atrial natriuretic peptide, rat; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains