Profiling of mRNA expression in quadriceps of patients with COPD and muscle wasting.
Peripheral muscle wasting is a feature of chronic obstructive pulmonary disease (COPD). Potent therapeutic strategies are needed to improve peripheral muscle mass in these patients. We hypothesized that the evaluation of the mRNA expression profile of quadriceps muscle could be useful in identifying key biochemical pathways involved in the wasting process. We monitored mRNA expression profile of quadriceps muscle in four patients with COPD with muscle atrophy (age: 71.3 +/- 2.1 years, mean SD; FEV(1) 28.3 +/- 10.8 % predicted) and four control subjects (age: 66.5 +/- 1.3 years) using HuU95v2 gene chips. Fifty-seven mRNAs transcripts (0.5%) were found to be differentially expressed in muscles of COPD patients (i.e., p < 0.01). Among them, forkhead box O -1 and -3 and insulin-like growth factor-1 expressions being significantly elevated in COPD subjects. Concomitantly, a significant reduction in mRNA expression of two myofilament proteins was observed. Energy production appears to be impaired as indicated by the significant rise in nicotinamide N-methyltransferase mRNA expression. This study provides for the first time evidence that genes are selectively expressed in limb muscles of COPD patients and further research need to focus on their functional roles in the pathogenesis of muscle dysfunction.
Debigaré
Richard
R
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Quebec, Canada. Richard.Debigare@rea.ulaval.ca
Maltais
François
F
Côté
Claude H
CH
Michaud
Annie
A
Caron
Marc-André
MA
Mofarrahi
Mahroo
M
Leblanc
Pierre
P
Hussain
Sabah N A
SN
D000368:Aged; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014797:Vital Capacity
D012333:RNA, Messenger