Increased Expression of Proinflammatory Genes in Peripheral Blood Cells Is Associated with Cardiac Cachexia in...

Area of Science:

• Cardiology
• Molecular Biology
• Metabolism

Background:

• Cardiac cachexia (CC) in chronic heart failure with reduced ejection fraction (HFrEF) is a catabolic state linked to poor prognosis.
• The role of specific transcription factors and signaling molecules in CC pathogenesis remains under-investigated.

Purpose of the Study:

• To investigate the expression of signal transducer and activator of transcription (STAT)1, STAT3, suppressor of cytokine signaling (SOCS)1, and SOCS3 in peripheral blood cells (PBC) of patients with CC.
• To correlate these molecular mediators with body composition, functional status, and skeletal muscle gene expression.

Main Methods:

• Gene expression analysis (qRT-PCR) in PBC from non-cachectic (ncCHF), cachectic (cCHF) HFrEF patients, and controls.
• Assessment of body composition (dual-energy X-ray absorptiometry) and inflammatory markers.
• Quantification of metabolic genes (SLC2A4) and protein degradation markers in skeletal muscle biopsies.

Main Results:

• Cachectic patients exhibited higher TNF and IL-10 expression, lower fat mass index (FMI), and lower fat-free mass index (FFMI).
• STAT1, STAT3, SOCS1, and SOCS3 expression were significantly elevated in PBC of cachectic patients compared to non-cachectic and control groups.
• In cachectic patients, elevated TNF and STAT1 expression correlated with reduced FMI, and skeletal muscle showed increased SLC2A4 expression.

Conclusions:

• Increased STAT1, STAT3, SOCS1, and SOCS3 expression in PBC suggests their involvement in the pathophysiology of cardiac cachexia.
• Elevated TNF and STAT-1 in peripheral blood are associated with reduced fat mass in cachectic heart failure patients.
• Upregulated SLC2A4 in skeletal muscle indicates altered glucose metabolism in cardiac cachexia.