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Multiple Signaling Axes (TNF-α/IL1β/IL8, TLR4/MYD88/NF-κB, and TGF-β1/ROS) Associated With Coronary Collateral

Yongjuan Zhao1, Hualan Zhou1, Ying Chen1

  • 1Department of Geriatrics, The Affiliated Huaian Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huaian 223002, China.

Mediators of Inflammation
|November 24, 2025
PubMed

Insights

Poor coronary collateral circulation (CCC) in elderly patients with coronary chronic total occlusion (CCTO) is linked to specific inflammatory and oxidative stress pathways. Reduced levels of these markers correlate with better CCC grades, suggesting their involvement in CCC impairment.

Area of Science:

  • Cardiovascular Medicine
  • Inflammation and Immunology
  • Geriatric Medicine

Background:

  • Poor coronary collateral circulation (CCC) is a significant issue in geriatric patients with coronary chronic total occlusion (CCTO).
  • Multiple signaling axes, including inflammatory and oxidative stress pathways, are suspected to contribute to impaired CCC.
  • Understanding these pathways is crucial for developing therapeutic strategies to improve CCC in this vulnerable population.

Purpose of the Study:

  • To investigate the relationship between poor CCC and key signaling axes in geriatric patients with CCTO.
  • To assess the expression levels of markers associated with pro-inflammatory, immune-inflammatory, and oxidative stress-inflammatory signaling pathways.
  • To determine if these markers correlate with the severity of CCC in patients with CCTO.

Main Methods:

  • Geriatric patients with CCTO were enrolled and categorized into CCC Grades 0, 1, and 2 based on contrast filling.
  • Simultaneous assessment of signaling axis markers: tumor necrosis factor-α (TNF-α), interleukin-1β (IL1β), IL8, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), nuclear factor kappa-B (NF-κB), transforming growth factor-β1 (TGF-β1), and reactive oxygen species (ROS).
  • Statistical analysis was performed to compare marker levels across different CCC grades.

Main Results:

  • Patients with CCC Grade 2 showed significantly decreased levels of TNF-α, IL1β, IL8, TLR4, MYD88, NF-κB, TGF-β1, and ROS compared to the CCC Grade 1 group (p < 0.002).
  • The CCC Grade 1 group exhibited lower levels of these markers than the CCC Grade 0 group (p < 0.002).
  • These findings indicate an inverse correlation between the severity of inflammatory and oxidative stress markers and the grade of CCC.

Conclusions:

  • The pro-inflammatory cytokine signaling axis (TNF-α/IL1β/IL8), immune-inflammatory signaling axis (TLR4/MYD88/NF-κB), and oxidative stress-inflammatory signaling axis (TGF-β1/ROS) play causative roles in impairing CCC.
  • These signaling pathways are implicated in the poor formation of CCC in geriatric patients with CCTO.
  • Targeting these axes may offer potential therapeutic avenues for improving coronary collateralization in CCTO patients.
Keywords:
coronary chronic total occlusioncoronary collateral circulationgeriatric patientsmultiple signaling axes

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