Expression of PIM1/ASK1 Molecular Pathway Related Genes in Ischemic Cardiomyopathy.

Abstract

Introduction: Myocardial ischemia/reperfusion injuries (MI/RI) are responsible for fatal cardiovascular diseases. Myocardial infarction may lead to ischemic cardiomyopathy (ICM). Thereby, illustrating the MI/RI molecular basis could lead to the emergence of novel therapeutic options. PIM1/ASK1 (MAP3K5) pathway is well-known in renal ischemia/ reperfusion. PIM1 protein can promote autophagy after hypoxia.

Materials and methods: We selected the dataset GSE46224 from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database for evaluation. This dataset was analyzed using tools such as the Kyoto Encyclopedia of Genes and Genomes, Gene- Codis, and BioGRID. Three groups of patients were selected from the dataset. ICM group (n=8), non-failing (NF) group (n=8), and non-ischemic cardiomyopathy (NICM) group (n=8) evaluated for 15 genes expression levels. P-value <0.05 is statistically significant.

Results: JAK1 showed significantly lower gene expression in the ICM group compared to the NF group (p-value = 0.012, difference = -6.24). ASK1 was also significantly down-regulated in the ICM group compared to the NF group (p-value =0.0159, difference = -1.478). In contrast, STAT5B and NF-κB were significantly up-regulated in the ICM group (STAT5B: p-value = 0.0238, difference = 2.388; NF-κB: p-value = 0.0158, difference = 1.11). The analysis of differences and the volcano plot confirmed these findings, highlighting key dysregulated genes in ICM.

Conclusion: In conclusion, ICM patients have altered ASK1 expression compared to NF individuals. The significant down-regulation of ASK1 and JAK1, along with the up-regulation of STAT5B and NF-κB, suggests that targeting ASK1 could be an important strategy to ameliorate ischemia-related cardiomyocyte damage.