Medical College of Wisconsin
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Pulsatile flow dynamics maintain pulmonary artery architecture. JCI Insight 2026 May 08;11(9)

Date

05/08/2026

Pubmed ID

42100871

Pubmed Central ID

PMC13232008

DOI

10.1172/jci.insight.201797

Scopus ID

2-s2.0-105038373018 (requires institutional sign-in at Scopus site)

Abstract

Single-ventricle congenital heart disease (SV-CHD) is a uniformly lethal condition requiring the Glenn surgery, which as a side effect eliminates arterial pulsatility and contributes to pulmonary vascular complications. In Glenn patients, we quantified pulsatility loss in each dimension of force (flow, pressure, and stretch) using cardiac catheterization and MRI. To model and investigate the individual impact of each dimension of pulsatility loss on the pulmonary vasculature, we applied isolated pulsatile and non-pulsatile mechanical stimuli to pulmonary artery endothelial cells (ECs) in vitro. We found that each dimension of force triggered distinct transcriptional responses, revealing force-specific regulation of structural and signaling pathways. Pulsatile stretch uniquely stimulated EC secretion of PDGFB, a key driver of vascular smooth muscle cell (vSMC) recruitment. In a rat Glenn model, loss of pulsatility led to vascular wall thinning, loss of EC PDGFB, and reduced activation of smooth muscle PDGFBRβ, confirming in vivo relevance. Our findings uncover a mechanistic link between endothelial stretch sensing and PDGFB-mediated EC-vSMC crosstalk, essential for maintaining pulmonary artery architecture. Clinically, these insights suggest that restoring or mimicking pulsatile forces may help preserve vascular integrity and prevent remodeling in patients with SV-CHD.

Author List

Spurgin SB, Thai L, Wan TC, Chaney CP, Cowdin MA, Reddy SV, Hussain T, Fares M, Iruela-Arispe ML, Carroll T, Spearman AD, Cleaver O

Authors

Andrew Spearman MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tina C. Wan Research Scientist II in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Disease Models, Animal
Endothelial Cells
Heart Defects, Congenital
Humans
Male
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Proto-Oncogene Proteins c-sis
Pulmonary Artery
Pulsatile Flow
Rats