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

Area of Science:

• Genomics
• Cardiovascular Research
• Metabolic Disorders

Background:

• Heart failure involves gene expression changes, but obesity-related high output heart failure (HOHF) lacks detailed transcriptomic study.
• Understanding HOHF pathophysiology is crucial due to its specific presentation in morbidly obese individuals.

Purpose of the Study:

• To investigate gene expression variances in leukocyte transcriptomes of morbidly obese patients with HOHF.
• To identify specific molecular pathways and regulators implicated in obesity-related HOHF.

Main Methods:

• Cross-sectional study design comparing 6 patients with HOHF and 6 with non-HOHF, all morbidly obese.
• Stranded total RNA-sequencing applied to leukocyte samples.
• Differential gene expression analysis and Ingenuity Pathway Analysis for pathway and network interpretation.

Main Results:

• Identified 116 differentially expressed genes in HOHF patients (114 upregulated, 2 downregulated).
• Affected genes and pathways relate to cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis.
• Top upregulated pathways include autophagy, AMPK signaling, and senescence; GATA binding protein 1 identified as an upstream regulator.

Conclusions:

• First report on differential gene expression in obesity-related HOHF, elucidating underlying pathophysiologic mechanisms.
• Highlights the role of cellular function, inflammation, and iron homeostasis in HOHF.
• Suggests further research to fully understand the molecular basis of HOHF.