Pulsatile flow dynamics maintain pulmonary artery architecture

Area of Science:

• Cardiovascular Research
• Pediatric Cardiology
• Vascular Biology

Background:

• Single-ventricle congenital heart disease (SV-CHD) is a severe condition necessitating the Glenn procedure.
• The Glenn surgery eliminates arterial pulsatility, leading to pulmonary vascular complications.

Purpose of the Study:

• To quantify pulsatility loss in Glenn patients across flow, pressure, and stretch dimensions.
• To investigate the impact of individual pulsatility loss dimensions on pulmonary vasculature using in vitro and in vivo models.

Main Methods:

• Cardiac catheterization and MRI were used to measure pulsatility in Glenn patients.
• Pulmonary artery endothelial cells (ECs) were subjected to pulsatile and non-pulsatile mechanical stimuli in vitro.
• A rat Glenn model was utilized to confirm in vivo findings.

Main Results:

• Each force dimension (flow, pressure, stretch) induced distinct transcriptional responses in ECs.
• Pulsatile stretch uniquely promoted EC secretion of PDGFB, crucial for vascular smooth muscle cell (vSMC) recruitment.
• Loss of pulsatility in vivo resulted in vascular wall thinning and reduced PDGFB signaling.

Conclusions:

• A mechanistic link exists between endothelial stretch sensing and PDGFB-mediated EC-vSMC crosstalk, vital for pulmonary artery structure.
• Restoring or mimicking pulsatile forces could be a therapeutic strategy to maintain vascular integrity in SV-CHD patients.