# Notch signaling enhances PASMC proliferation and vascular remodeling in CTEPH

## TL;DR

This study shows that Notch signaling promotes lung artery thickening in a rat model of CTEPH, and blocking it could be a treatment option.

## Contribution

The study identifies Notch signaling as a novel therapeutic target for CTEPH by linking it to vascular remodeling.

## Key findings

- Notch pathway proteins (Notch1, Notch3, Jagged1, Hes1) are elevated in CTEPH rats.
- DAPT treatment reduced Notch signaling and mitigated vascular remodeling in CTEPH.
- Notch signaling promotes PASMC proliferation and contributes to PVR in CTEPH.

## Abstract

The Notch signaling pathway is implicated in pulmonary vascular remodeling (PVR) in Chronic Thromboembolic Pulmonary Hypertension (CTEPH). This study investigated the role of Notch signaling in PVR using a rat model of CTEPH and performed measurements including Right Ventricular Systolic Pressure (RVSP), Mean Pulmonary Arterial Pressure (MPAP), and histological analysis of pulmonary small arteries. Western blot analysis revealed elevated levels of Notch1, Notch3, Jagged1, and Hes1 proteins in CTEPH rats. Furthermore, the Notch pathway proteins (Notch1, Notch3, Jagged1, and Hes1) were even more elevated in the CTEPH + VPA group. In contrast, protein levels were reduced in the CTEPH + DAPT (a γ-secretase inhibitor) group. The medial wall thickness percentage (MWT%) and markers of smooth muscle cell proliferation, including PCNA and α-SMA, were significantly increased in the CTEPH and CTEPH + VPA groups and decreased after DAPT treatment. These findings suggest that activation of the Notch signaling pathway promotes the proliferation of Pulmonary Artery Smooth Muscle Cells (PASMCs), contributing to PVR in CTEPH. Inhibition of Notch signaling with DAPT mitigated vascular remodeling, suggesting a potential therapeutic target for CTEPH.