Differences in Leukocyte Transcriptomes of Morbidly Obese Patients With High Output Heart Failure: A Pilot Study

Abstract

Background and Objectives Heart failure is characterized by alterations of gene expression that provide insight into the underlying pathophysiologic mechanisms. However, obesity-related high output heart failure (HOHF) is a specific phenotype of heart failure that has not been studied using gene expression. Our aim in this study was to examine the variances in leukocyte transcriptomes of morbidly obese patients with HOHF. Methods In this cross-sectional study, we applied stranded total RNA-sequencing to six patients with morbid obesity and HOHF and 6 patients with morbid obesity and non-HOHF. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and networks in these patients. Results We found in patients with HOHF that there were 116 differentially expressed genes with upregulation of 114 genes and downregulation of 2 genes. The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. We identified GATA binding protein 1 as an upstream regulator and nuclear factor kappa-light-chain-enhancer of activated B cells associated network. Conclusions We are the first to report the differential gene expression in patients with obesity-related HOHF and reveal the various pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Novel Insights Into the Pathogenesis of Obesity-Related High Output Heart Failure From Gene Expression Profiling

“…In the latest issue of the International Journal of Heart Failure , Cintron et al 9) conducted a pilot and cross-sectional study to examine the variances in leukocyte transcriptomes of morbidly obese patients with HOHF and attempted to provide insight into the underlying pathophysiologic mechanisms. Gene expression analyses showed the upregulation of 114 genes and downregulation of 2 genes in morbidly obese and HOHF patients compared to the gene expressions in morbidly obese and non-HOHF patients.…”