Key result
In idiopathic pulmonary arterial hypertension, pulmonary artery smooth muscle cells and adventitial fibroblasts retain their cellular identities but acquire distinct disease-associated states, with PASMC showing heightened glycosaminoglycan production and PAAF displaying a hyperproliferative phenotype.
Why the study?
The mechanisms driving the transition of pulmonary artery smooth muscle cells and adventitial fibroblasts to a diseased phenotype in pulmonary vascular remodeling remain elusive.
Highlights potential cell-state targets in IPAH; leaves open causal validation and clinical translation.
Summary 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.
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Crnković et al. (2025) studied Idiopathic pulmonary arterial hypertension. Idiopathic pulmonary arterial hypertension (disease state) vs. Healthy downsized lung donors was evaluated on Transcriptomic and proteomic profiling of cell states. In idiopathic pulmonary arterial hypertension, pulmonary artery smooth muscle cells and adventitial fibroblasts retain their cellular identities but acquire distinct disease-associated states, with PASMC showing heightened glycosaminoglycan production and PAAF displaying a hyperproliferative phenotype.
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