Multicellular Crosstalk and Therapeutic Vaccines in Heart Failure

Area of Science:

• Cardiovascular Biology
• Immunology
• Systems Biology

Background:

• Heart failure (HF) is a major global health challenge with current treatments primarily focusing on neurohumoral pathways, neglecting intrinsic cardiac remodeling processes.
• Advances in omics and systems biology reveal HF as a complex multicellular syndrome driven by disrupted intercellular communication within the cardiac cellular ecosystem.
• Pathological cardiac remodeling arises from maladaptive signaling networks among cardiomyocytes, endothelial cells, fibroblasts, and immune cells.

Purpose of the Study:

• To review emerging trends in heart failure research, integrating advances in multicellular biology and therapeutic vaccination.
• To propose immunization as a novel, unifying strategy to target the root causes of cardiac remodeling in heart failure.
• To explore how targeting intercellular communication can lead to disease-modifying therapies for HF.

Main Methods:

• Review of recent progress in genetics, single-cell and spatial omics, and systems biology related to HF.
• Analysis of circulating biomarkers reflecting cellular senescence, inflammation, fibrosis, and metabolic stress in HF.
• Integration of findings on specific mediators like insulin-like growth factor-binding protein 7 and signaling pathways such as MYC-CXCL1-CXCR2.

Main Results:

• Insulin-like growth factor-binding protein 7 links endothelial cell senescence to cardiomyocyte metabolic dysfunction.
• Specific fibroblast subpopulations promote HF progression via paracrine signaling pathways.
• Immunization strategies targeting intercellular communication show promise in preclinical and early clinical studies for HF.

Conclusions:

• Targeting pathological intercellular communication represents a novel therapeutic paradigm for heart failure.
• Immunization-based therapies, including peptide vaccines, offer a promising approach to modify HF progression by addressing cardiac remodeling at its source.
• This review proposes immunization as a unifying strategy for disease-modifying heart failure therapy.