Integrating Literature-Based Knowledge Database and Expression Data to Explore Molecular Pathways Connecting PPARG and Myocardial Infarction

Abstract

Peroxisome proliferator-activated receptor γ (PPARG) might play a protective role in the development of myocardial infarction (MI) with limited mechanisms identified. Genes associated with both PPARG and MI were extracted from Elsevier Pathway Studio to construct the initial network. The gene expression activity within the network was estimated through a mega-analysis with eight independent expression datasets derived from Gene Expression Omnibus (GEO) to build PPARG and MI connecting pathways. After that, gene set enrichment analysis (GSEA) was conducted to explore the functional profile of the genes involved in the PPARG-driven network. PPARG demonstrated a significantly low expression in MI patients (LFC=−0.52; p<1.84e−9). Consequently, PPARG could indicatively be promoting three MI inhibitors (e.g., SOD1, CAV1, and POU5F1) and three MI-downregulated markers (e.g., ALB, ACADM, and ADIPOR2), which were deactivated in MI cases (p<0.05), and inhibit two MI-upregulated markers (RELA and MYD88), which showed increased expression levels in MI cases (p=0.0077 and 0.047, respectively). These eight genes were mainly enriched in nutrient- and cell metabolic-related pathways and functionally linked by GSEA and PPCN. Our results suggest that PPARG could protect the heart against both the development and progress of MI through the regulation of nutrient- and metabolic-related pathways.

Integrative Analysis of Key Candidate Genes and Signaling Pathways in Acute Coronary Syndrome Related to Obstructive Sleep Apnea by bioinformatics

“…PPARG is a member of the nuclear hormone receptor superfamily, which can recruit transcriptional coactivators necessary to initiate the transcription of target genes and may also play a protective role in the development of MI 34,35 . At the same time, Cao et al also con rmed that THERE was a signi cant correlation between PPARG and protection of MI 36 .…”

Exploring Disrupted Gene Networks in Human 22q11.2 Microdeletion

“…Yy1 heterozygous mice exhibit growth retardation, neurulation defects, intellectual disability, and brain abnormalities [53,55]. PPARG regulates circadian cardiovascular rhythms and appears to have a cardioprotective effect [56][57][58]. PAX6 regulates the development of the central nervous system, and a patient with mental disorder had a deletion in the adjacent region of this gene [59][60].…”

Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics

“…Moreover, previous evidence has suggested that PPARG may be a risk factor for cardiovascular diseases such as metabolic syndrome, obesity, diabetes and hypertension 34 – 37 . PPARG is a member of the nuclear hormone receptor superfamily, which can the recruit the transcriptional coactivators necessary to initiate the transcription of target genes and may also play a protective role in the development of MI in many studies 38 – 39 . At the same time, previous studies have also found that PPARG may play an important role in the pathophysiological mechanism of OSA 40 , 41 , and qPCR detection suggests that the expression of PPARG in OSA patients is significantly different from that in the control group 42 .…”