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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Crnkovic, S; Thekkekara, Puthenparampil, H; Mulch, S; Biasin, V; Radic, N; Wilhelm, J; Bartkuhn, M; Bonyadi, Rad, E; Wawrzen, A; Matzer, I; Mitra, A; Leib, RD; Nagy, BM; Sahu-Osen, A; Valzano, F; Bordag, N; Evermann, M; Hoetzenecker, K; Olschewski, A; Ljubojevic-Holzer, S; Wygrecka, M; Stenmark, K; Marsh, LM; de, Jesus, Perez, V; Kwapiszewska, G.
Adventitial fibroblasts direct smooth muscle cell-state transition in pulmonary vascular disease.
Elife. 2025; 13:
Doi: 10.7554/eLife.98558
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- Leading authors Med Uni Graz
- Crnkovic Slaven
- Kwapiszewska-Marsh Grazyna
- Co-authors Med Uni Graz
- Biasin Valentina
- Bonyadirad Ehsan
- Bordag Natalie
- Holzer Senka
- Marsh Leigh
- Matzer Ingrid
- Nagy Miklos Bence
- Olschewski Andrea
- Radic Nemanja
- Sahu-Osen Anita
- Thekkekara Puthenparampil Helene
- Valzano Francesco
- Wawrzen Alicja
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- Abstract:
- BACKGROUND: Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs). Mechanisms driving the transition to a diseased phenotype remain elusive. METHODS: We combined transcriptomic and proteomic profiling with phenotypic characterization of source-matched cells from healthy controls and individuals with idiopathic pulmonary arterial hypertension (IPAH). Bidirectional cellular crosstalk was examined using direct and indirect co-culture models, and phenotypic responses were assessed via transcriptome analysis. RESULTS: PASMC and PAAF undergo distinct phenotypic shifts during pulmonary vascular remodeling, with limited shared features, such as reduced mitochondrial content and hyperpolarization. IPAH-PASMC exhibit increased glycosaminoglycan production and downregulation of contractile machinery, while IPAH-PAAF display a hyperproliferative phenotype. We identified alterations in extracellular matrix components, including laminin and collagen, alongside pentraxin-3 and hepatocyte growth factor, as potential regulators of PASMC phenotypic transitions mediated by PAAF. CONCLUSIONS: While PASMCs and PAAFs retain their core cellular identities, they acquire distinct disease-associated states. These findings provide new insights into the dynamic interplay of pulmonary vascular mesenchymal cells in disease pathogenesis. FUNDING: This work was supported by Cardio-Pulmonary Institute EXC 2026 390649896 (GK) and Austrian Science Fund (FWF) grant I 4651-B (SC).
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Myocytes, Smooth Muscle - physiology, metabolism, pathology
- Fibroblasts - physiology, metabolism, pathology
- Adventitia - pathology
- Pulmonary Artery - pathology
- Male - administration & dosage
- Vascular Remodeling - administration & dosage
- Female - administration & dosage
- Cells, Cultured - administration & dosage
- Familial Primary Pulmonary Hypertension - pathology
- Adult - administration & dosage
- Find related publications in this database (Keywords)
- pulmonary artery
- adventitial fibroblasts
- vascular smooth muscle cells