Global gene expression profiling in the failing myocardium.
Heart failure (HF) is a syndrome that involves multiple cellular mechanisms leading to a common phenotype of reduced ventricular contraction and cardiac chamber dilation. To clarify the mechanisms, a number of microarray analyses of the failing myocardium have been conducted. Gene expression profiles are usually compared between opposing pairs of samples, such as non-failing vs failing hearts, ischemic vs non-ischemic hearts, male vs female failing hearts or atria vs ventricles of failing hearts. Apart from these conventional methods, a different novel approach identified cardiac myosin light chain kinase (MLCK) as a HF-related gene by the comprehensive search for the genes that had an expression level that strongly correlated with the severity of HF; further investigations proved the important role of cardiac MLCK in HF. Moreover, a robust gene expression signature composed of 27 genes was revealed on analysis of 4 independent microarray data sets from the failing myocardium of dilated cardiomyopathy. The authors newly demonstrate 107 HF-related genes that were listed in 2 or more of 7 microarray data sets previously reported. Among these genes, many were observed to be involved in mitochondrial dysfunction and oxidative phosphorylation and 3 extracellular molecules, including periostin, pleiotrophin, and SERPINA3, which might become novel diagnostic and therapeutic targets for HF. These novel strategies warrant the new identification of specific genes that are linked to the pathophysiology of HF.
Asakura
Masanori
M
Department of Research and Development of Clinical Research, National Cardiovascular Center, Suita, Japan. masakura@hsp.ncvc.go.jp
Kitakaze
Masafumi
M
D002311:Cardiomyopathy, Dilated / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D030541:Databases, Genetic; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D015843:Serpins / Q000235:genetics; D012720:Severity of Illness Index
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005819:Genetic Markers; C512835:POSTN protein, human; C516148:SERPINA3 protein, human; D015843:Serpins; C066845:pleiotrophin; D009219:Myosin-Light-Chain Kinase