Objective: To investigate the ion channel genes related with the genesis and development of heart failure after myocardial infarction through analyzing the differential gene expressions in non-infarcted myocardial tissues of post-myocardial infarction heart failure (PIHF) rat model, and that of normal rat, and the bio-informatics Stc-GO analysis on them.
Methods: Rat model of PIHF was established by left anterior descending coronary artery ligation in six SD rats, and a control group with six sham-operative rats was set. Myocardial samples were taken in two batches from them (three rats in each group) at the heart failure formation stage and the stable stage (10 days and 8 weeks after operation) respectively. Total RNA extraction, probe preparation with reverse transcription, hybridization with double-channel cDNA microarray of rat's ion channel genes, and computerized differential gene expression screening were conducted, and Stc-GO functional clustering analysis was performed on the outcomes obtained to search out the GO sort of significance in them.
Results: At 10 days after operation, 319 common differential expressed genes were found from the 746 target genes, all of them were up-regulated. At 8 weeks after operation, in the 276 differential expressed genes, 274 were up-regulated while the other two down-regulated. The up-regulated genes were those concerning receptors of various hormones, cytokines, neuro-hormones, growth factors and nuclear receptor, protein phosphorylase, G protein, various ion channels mediated by ligand or voltage, transport protein, receptor interfering protein, etc. The down-regulated genes concerning the potassium channel and transport protein, etc. Stc-GO analysis found that the six genes concerning adrenergic receptor kinase beta 1 (betaARK1), amiloride-sensitive cation channel 2 neuronal (Accn2), voltage-dependent calcium ion channel gamma subunit 1 (Cacng1), cyclic nucleotide gated channel alpha 1 (Cnga1), Glutamate receptor ionotropic kainite 2 (Grik 2) and neurotrophic tyrosine kinase receptor type 2 (Ntrk 2), were all the significantly up-regulated differential genes of the model group related with the sham-operative group, and all showed a down-regulating trend as time goes on, and four genes in them were validated by the RT-PCR test.
Conclusion: Ion channel genes concerning Accn2, Grik2, Ntrk2 and Cacng1 were up-regulated in PIHF, and its mechanism is waiting for further study.