Author response: Adventitial fibroblasts direct smooth muscle cell-state transition in pulmonary vascular disease
Year: 2025
Type: peer-review
Abstract: Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to a diseased phenotype remain elusive. Utilizing a combination of transcriptomic and proteomic profiling, along with phenotyping of source-matched cells from healthy controls and individuals with idiopathic pulmonary arterial hypertension (IPAH), our investigation uncovered that while PASMC and PAAF retained their original cellular identities, they acquired distinct disease-associated states. Though both cell types exhibited reduced mitochondrial content and hyperpolarization, IPAH-PASMC displayed heightened glycosaminoglycan production and downregulation of contractile machinery, contrasting a hyperproliferative phenotype of IPAH-PAAF. We investigated the involvement of cellular crosstalk in regulating cell state dynamics and identified pentraxin-3 and hepatocyte growth factor as potential modulators of PASMC phenotypic transition orchestrated by PAAF. Our findings contribute to a deeper understanding of pulmonary vascular mesenchyme dynamics in disease pathogenesis.
Authors: Slaven Crnkovic, Helene Thekkekara Puthenparampil, Shirin Mulch, Valentina Biasin, Nemanja Radic, Jochen Wilhelm, Marek Bartkuhn, Ehsan Bonyadi Rad, Alicja Wawrzen, Ingrid Matzer, Ankita Mitra, Ryan Leib, Bence M Nagy, Anita Sahu-Osen, Francesco Valzano, Natalie Bordag, Matthias Evermann, Konrad Hoetzenecker, Andrea Olschewski, Senka Ljubojevic-Holzer, Malgorzata Wygrecka, Kurt Stenmark, Leigh M Marsh, Vinicio de Jesus Perez, Grazyna Kwapiszewska
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4408057882