CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID

Area of Science:

• Cardiovascular Biology
• Infectious Diseases
• Immunology

Background:

• The endothelium's role in long coronavirus disease (COVID) cardiac injury is recognized, yet mechanisms are unclear.
• Endothelial cells (ECs) are crucial for vascular health and can be affected by viral infections.

Purpose of the Study:

• To elucidate the mechanisms by which endothelial dysfunction contributes to cardiac injury in long COVID.
• To identify specific molecular mediators linking endothelial cells to cardiac dysfunction post-SARS-CoV-2 infection.

Main Methods:

• Utilized patient-derived thrombotic vascular tissues and induced pluripotent stem cell-derived ECs (iPSC-ECs) to model endotheliitis.
• Developed cardiac organoids (iPSC-ECs and cardiomyocytes) for functional assessment post-SARS-CoV-2 exposure.
• Performed single-cell chromatin accessibility and gene expression profiling, high-throughput proteomics, and animal model studies.

Main Results:

• Endotheliitis in long COVID models showed cytokine upregulation, particularly CCL2.
• Cardiac organoids exposed to SARS-CoV-2 exhibited dysfunction mediated by CCL2.
• CCL2 was linked to 'phenotype switching' and cardiac dysfunction via oxidative stress and protein modification in cardiac cells.

Conclusions:

• Endothelial cell-released cytokines, especially CCL2, are key contributors to cardiac dysfunction in long COVID.
• These findings underscore the significance of vascular health monitoring in long COVID patients.
• Targeting CCL2-mediated pathways presents a potential therapeutic avenue for long COVID-related cardiac complications.