Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function

Area of Science:

• Genetics
• Immunology
• Cardiology

Background:

• Inflammation plays a role in cardiovascular disease (CVD) pathogenesis, but causal links of specific inflammatory cytokines are not fully understood.
• Mendelian randomization (MR) offers a robust approach to investigate etiological insights into CVD, overcoming limitations of traditional research methods.

Purpose of the Study:

• To investigate the causal relationships between 91 circulating inflammatory proteins and various CVD outcomes and cardiac remodeling.
• To identify specific inflammatory cytokines that may serve as therapeutic targets for CVD prevention and treatment.

Main Methods:

• A large-scale Mendelian randomization (MR) study utilizing summary-level genetic data.
• Analysis of 91 inflammatory proteins in relation to diverse CVD outcomes including coronary artery disease, stroke, atrial fibrillation, heart failure, and cardiac remodeling parameters.
• Primary analysis employed the inverse-variance weighted method, supplemented by several sensitivity analyses.

Main Results:

• Hepatocyte growth factor (HGF) showed a causal link with increased risk for any stroke and ischemic stroke.
• Programmed cell death 1 ligand 1 (PD-L1) was associated with a reduced risk of atrial fibrillation.
• Several proteins (CCL20, CDCP1, Flt3L, IL-10RA) were identified as causal risk factors for coronary artery disease, while others (LIF, ST1A1) demonstrated protective effects. IL-4 and LIF-R were linked to changes in right heart function.

Conclusions:

• The study identifies specific circulating inflammatory cytokines with potential causal roles in CVD development and progression.
• These findings nominate novel targets for the development of CVD treatments and preventative strategies.
• Further research is needed to elucidate underlying mechanisms and facilitate clinical translation.