Identification of altered pathways in hypertrophic cardiomyopathy based on combined data of protein-protein interactions and molecular pathways

Abstract

ABSTRACT. The purpose of our study was to identify molecular pathways altered during the pathogenesis of hypertrophic cardiomyopathy (HCM) based on data from the STRING proteinprotein interaction (PPI) database and the REACTOME pathway database. Identification of differentially expressed genes (DEGs) was carried out, followed by construction of a targeted network and selection of hub genes in this network. PPI pairs in each pathway were extracted, and altered pathways were identified when the said pathway differed from common interactions within the targeted network with a P value of less than 0.05. These altered pathways were further validated based on enrichment of hub genes in pathways within the targeted network. Through this method, we identified 1085 DEGs. The DEGs were inputted into the STRING database, and the resulting targeted network was composed of 3631 interactions. Based on the selection criteria, 30 significantly changed pathways were screened in total. Among these, the top five pathways were found to be involved in immune modulation, signal transduction, hemostasis, and G protein-coupled receptor signaling. Similarly, enrichment in hub gene interactions was also found in members within the altered pathways, including those involved in the innate immune system, the immune system, and signal transduction pathways. These altered pathways are important for understanding the underlying mechanisms of HCM, and can be used for clinical application of treatments in the future.

RNA‐seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy

“…To the best of our knowledge, this is the first study that demonstrates the existence of distinctive pathways modifications between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level. The results obtained on isolated cardiomyocytes are overlapping, at least partially, with previous studies analyzing HCM myocardial homogenates 52–55 . This might reflect the relative abundance of cardiomyocytes in the myocardial samples.…”

“…In recent years, whole transcriptome investigations by performing focused RNA‐seq experiments and/or analyzing related datasets available in specialized online repositories revealed altered gene‐expression profiles in HCM. Reported gene‐enriched pathways involve immune modulation, signal transduction, hemostasis, metabolism, muscle contraction, inflammation, and fibrosis (TGF‐β pathways) 52–55 …”

“…Reported gene-enriched pathways involve immune modulation, signal transduction, hemostasis, metabolism, muscle contraction, inflammation, and fibrosis (TGFβ pathways). [52][53][54][55] Results published so far are based on the analysis of whole myocardial samples, including cardiomyocytes, vessels, fibroblasts, and interstitial tissue, and do not provide information on the possible existence of expression profiles selectively related to coronary microvascular dysfunction.…”

Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation

“…The topological centralities, including the local scale (degree) and the global scale (betweenness, closeness and stress), were extensively utilized in the network analysis. Of these, degree is a simple and evident measure that defines the number of links between a node and its neighboring nodes ( 27 ). In the present study, nodes with a certain degree were proposed to be hub genes ( 28 , 29 ).…”

Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

“…HCM is characterized by the enlarged heart, abnormal thickened left ventricular (LV) walls, and chamber capacity reduction in the absence of other causes, such as hypertension or aortic stenosis [3–5]. Recently, increasing evidence has demonstrated that the immune system and multiple pro‐inflammatory factors play a fundamental role in the pathogenesis of HCM [6]. Toll‐like receptor‐4 ( TLR4 ) is a family member of pattern recognition receptors that play important roles in mediating the inflammatory response [7–9].…”