# Blocking AREG-EGFR signaling attenuates pan-arterial fibrosis in chronic cardiac allograft rejection

## TL;DR

This study shows that blocking AREG-EGFR signaling reduces fibrosis in arteries affected by chronic heart transplant rejection.

## Contribution

The study identifies AREG-EGFR signaling as a novel therapeutic target for pan-arterial fibrosis in cardiac allograft vasculopathy.

## Key findings

- Fibrosis is widespread in aorta, pulmonary artery, and coronary artery in CAV.
- T cells promote fibroblast activation through AREG-EGFR signaling.
- Blocking AREG-EGFR reduces fibrosis in mouse models of arterial transplantation.

## Abstract

Cardiac allograft vasculopathy (CAV) is a major barrier to long-term survival after heart transplantation, characterized by progressive vascular remodeling and luminal narrowing. Fibrosis is one of the key pathological features of CAV progression, but its underlying mechanisms remain unclear. This study aims to investigate the mechanisms of CAV-associated vascular fibrosis and explore potential therapeutic targets.

Clinical specimens from the aorta (AO), pulmonary artery (PA), and coronary artery (CA) of CAV and control (Ctrl) groups were analyzed using single-cell RNA sequencing (scRNA-seq). Further validation was performed using a mouse arterial transplantation model.

This study found that vascular fibrosis occurs extensively in AO, PA, and CA, rather than being confined to CA alone. scRNA-seq analysis revealed that increased fibroblasts (FBs) and extracellular matrix (ECM) remodeling are common features across all three vascular regions. Cell-cell interaction analysis showed that T cells promote FB activation via AREG-EGFR. Two murine transplantation models further confirmed that blocking AREG-EGFR signaling significantly reduces fibrosis.

Pan-arterial fibrosis represents a unifying pathological process across major vascular territories in CAV. Targeting fibrotic remodeling may offer a promising adjunctive strategy to improve long-term graft outcomes.