Related Experiment Video
Updated: Jul 4, 2025
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Increased Expression of Proinflammatory Genes in Peripheral Blood Cells Is Associated with Cardiac Cachexia in
Anja Sandek1,2, Christoph Gertler1,2, Miroslava Valentova1,2
1Department of Cardiology and Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Insights
Cardiac cachexia (CC) in chronic heart failure with reduced ejection fraction (HFrEF) involves increased STAT1, STAT3, SOCS1, and SOCS3 expression in peripheral blood cells. This correlates with lower fat mass in cachectic patients and altered glucose metabolism in skeletal muscle.
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.
Abstract:
Background: Cardiac cachexia (CC) in chronic heart failure with reduced ejection fraction (HFrEF) is characterized by catabolism and inflammation predicting poor prognosis. Levels of responsible transcription factors like signal transducer and activator of transcription (STAT)1, STAT3, suppressor of cytokine signaling (SOCS)1 and SOCS3 in peripheral blood cells (PBC) are underinvestigated in CC. Expression of mediators was related to patients' functional status, body composition (BC) and metabolic gene expression in skeletal muscle (SM). Methods: Gene expression was quantified by qRT-PCR in three cohorts: non-cachectic patients (ncCHF, n = 19, LVEF 31 ± 7%, BMI 30.2 ± 5.0 kg/m2), cachectic patients (cCHF; n = 18, LVEF 27 ± 7%, BMI 24.3 ± 2.5 kg/m2) and controls (n = 17, LVEF 70 ± 7%, BMI 27.6 ± 4.6 kg/m2). BC was assessed by dual-energy X-ray absorptiometry. Blood inflammatory markers were measured. We quantified solute carrier family 2 member 4 (SLC2A4) and protein degradation by expressions of proteasome 20S subunit beta 2 and calpain-1 catalytic subunit in SM biopsies. Results: TNF and IL-10 expression was higher in cCHF than in ncCHF and controls (all p < 0.004). cCHF had a lower fat mass index (FMI) and lower fat-free mass index (FFMI) compared to ncCHF and controls (p < 0.05). STAT1 and STAT3 expression was higher in cCHF vs. ncCHF or controls (1.1 [1.6] vs. 0.8 [0.9] vs. 0.9 [1.1] RU and 4.6 [5.5] vs. 2.5 [4.8] vs. 3.0 [4.2] RU, all ANOVA-p < 0.05). The same applied for SOCS1 and SOCS3 expression (1.1 [1.5] vs. 0.4 [0.4] vs. 0.4 [0.5] and 0.9 [3.3] vs. 0.4 [1.1] vs. 0.8 [0.9] RU, all ANOVA-p < 0.04). In cCHF, higher TNF and STAT1 expression was associated with lower FMI (r = 0.5, p = 0.053 and p < 0.05) but not with lower FFMI (p > 0.4). In ncCHF, neither cytokine nor STAT/SOCS expression was associated with BC (all p > 0.3). SLC2A4 was upregulated in SM of cCHF vs. ncCHF (p < 0.03). Conclusions: Increased STAT1, STAT3, SOCS1 and SOCS3 expression suggests their involvement in CC. In cCHF, higher TNF and STAT-1 expression in PBC were associated with lower FMI. Increased SLC2A4 in cachectic SM biopsies indicates altered glucose metabolism.
Related Concept Videos
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:17Pathophysiology of Heart Failure
01:26Imbalances in Cardiac Output
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...