ABSTRACT
After myocardial infarction (MI) occurs, progressive pathological cardiac remodeling results in heart dysfunction and even heart failure during the following months or years. The present study explored the molecular mechanisms underlying the late phase of MI at the global transcript level. A rhesus monkey model of myocardial ischemia induced by left anterior descending (LAD) artery ligation was established, and the heart tissue was collected eight weeks after ligation for transcriptome analysis by DNA microarray technology. Differentially expressed genes in the core infarcted area and remote infarcted area of the ischemic heart were detected with significance analysis of microarray (SAM), and related pathways were detected by Gene Ontology (GO)/pathway analysis. We found that compared to the sham condition, prolonged ischemia increased the levels of 941 transcripts, decreased the levels of 380 transcripts in the core infarcted area, and decreased the levels of 8 transcripts in the remote area in monkey heart tissue. Loss of coordination between the expression of genes, including natriuretic peptide A (NPPA), NPPB, and corin (Corin, serine peptidase), may aggravate cardiac remodeling. Furthermore, imbalance in the enriched significantly changed pathways, including fibrosis-related pathways, cardioprotective pathways, and the cardiac systolic pathway, likely also plays a key role in regulating the development of heart remodeling.
Subject(s)
Myocardial Infarction , Myocardial Ischemia , Animals , Macaca mulatta , Ventricular Remodeling/genetics , Heart , Myocardial Ischemia/pathology , Myocardial Infarction/pathology , Gene Expression , Myocardium/pathology , Disease Models, AnimalABSTRACT
Genome sequencing and bioinformatics is driving the discovery of drug targets and development of novel classes of broad spectrum antimicrobial compounds. The analysis of the complete genome sequences of microorganism available in the public databases offers the first insights into the drug targets discovery. This review discusses the use of genomic information in the finding of target genes for antimicrobial drug discovery.
