ABSTRACT
Heart failure is the leading cause of mortality in Western society and represents the fastest growing subclass of cardiovascular diseases. An increasing body of evidence indicates an important role for microRNAs (miRNAs) in the pathogenesis and progression of heart failure. miRNAs are small noncoding RNAs that regulate expression of target genes by sequence-specific binding to the 3' untranslated region of messenger RNA, which results in degradation or translational repression. To date, many miRNAs (and their targets) that play a role in diverse aspects of cardiac remodeling and heart failure development have been identified. Here, we give an overview of these miRNAs and their role in cardiac pathogenesis. In addition, we provide brief insight into the potential of miRNAs as novel therapeutic targets for heart failure.
Subject(s)
Gene Expression Regulation/drug effects , Heart Failure/drug therapy , MicroRNAs/drug effects , Molecular Targeted Therapy/trends , Cardiomegaly/drug therapy , Cardiomegaly/genetics , Endomyocardial Fibrosis/drug therapy , Endomyocardial Fibrosis/genetics , Excitation Contraction Coupling/drug effects , Excitation Contraction Coupling/genetics , Gene Expression Regulation/genetics , Heart Failure/genetics , Humans , MicroRNAs/genetics , Models, Cardiovascular , Ventricular Remodeling/drug effects , Ventricular Remodeling/geneticsABSTRACT
RATIONALE: Altered expression of glutamate transporter EAAT2 protein has been reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis. METHODS: By RT-PCR we studied the occurrence of I7R and E9S in neocortical and hippocampal specimens from TLE patients and non-neurological controls. RESULTS: Both splice forms were found in all neocortical specimens from TLE patients (100% I7R, 100% E9S). This was significantly more than in controls (67% I7R, 60% E9S; P < 0.05). We also detected I7R and E9S in all seven motor cortex post-mortem samples from patients with amyotrophic lateral sclerosis. Within the TLE patient group, both splice variants appeared significantly more in non-sclerotic (100%), than in sclerotic hippocampi (69%, P < 0.05). CONCLUSION: These data indicate that the epileptic brain, especially that of TLE patients without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA splicing. Our data confirm that the presence of alternative EAAT2 splice forms is not disease specific.
