Transcriptional landscape of pulmonary artery endothelium reveals subpopulation- and disease-specific remodeling signatures
The physiological state of endothelial cells (ECs) is a central determinant of organ health. Distinct endothelial phenotypes and transcriptional programs are linked to vessel size and anatomical location, but it remains unclear how this intrinsic heterogeneity is organized within a particular niche. We performed compartment-specific single-cell profiling of human pulmonary artery (PA) ECs from healthy donors and from patients with two clinically divergent forms of pulmonary hypertension (PH): pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with pulmonary fibrosis (PH-PF). We identified and localized three major EC subsets in healthy and remodeled PAs termed immuno-, vascular tone- and vascular plasticity modulatory, reflecting their enrichment for distinct biological processes. Expression signatures defining each subset were shared with other arterial beds, including the aorta and coronary arteries, and murine PA. Both PAH and PH-PF altered PAEC subset compositions, with increased immunomodulatory and decreased vascular plasticity modulatory PAECs. PH-PF PAECs were generally defined by dysregulated angiogenesis and antigen presentation, whereas PAH PAECs exhibited lipid metabolic dysfunction and enhanced vasoregulatory signaling. By uncovering endothelial heterogeneity and pathology-specific transcriptional programs in PAs, this study underscores the need of disease-specific therapeutic targeting.
Authors
- Alberto Benazzo (ORCID: https://orcid.org/0000-0002-3549-4720)
- Edward Cantu (ORCID: https://orcid.org/0000-0003-1105-0129)
- Grażyna Kwapiszewska (ORCID: https://orcid.org/0000-0003-0518-9079)
- Slaven Crnković (ORCID: https://orcid.org/0000-0002-0820-3318)
- Marek Bartkuhn (ORCID: https://orcid.org/0000-0001-6872-9082)
- Izabela Borek (ORCID: https://orcid.org/0000-0002-2527-6199)
- Leigh Marsh (ORCID: https://orcid.org/0000-0002-4613-1538)
- Elisabeth Fließer (ORCID: https://orcid.org/0000-0002-2203-2981)
- Edward E. Morrisey (ORCID: https://orcid.org/0000-0001-5785-1939)
- Anna Birnhuber (ORCID: https://orcid.org/0000-0002-8358-8377)
- Clemens Aigner (ORCID: https://orcid.org/0000-0002-7787-991X)
- Francesco Valzano
- Jörg Lindenmann
- Thomas Lins
- Nikolaus Kneidinger
- Maria C. Basil (ORCID: https://orcid.org/0000-0003-4716-1285)
- Jeremy Katzen
- Jonas C. Schupp (ORCID: https://orcid.org/0000-0002-7714-8076)
- Mike Morley
Institutions
- Medical University of Graz (AT)
- Yale University (US)
- Medizinische Hochschule Hannover (DE)
- Penn Center for AIDS Research (US)
- German Center for Lung Research (DE)
- Universities of Giessen and Marburg Lung Center (DE)
- Cardio-Pulmonary Institute (DE)
- Medical University of Vienna (AT)
- University of Pennsylvania (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Communications Biology
- Published
- 2026-05-11
- DOI
- https://doi.org/10.1038/s42003-026-10204-0
- Primary Topic
- Pulmonary Hypertension Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Respiratory Society
- Deutsche Forschungsgemeinschaft
- Austrian Science Fund
- Karl-Franzens-Universität Graz
- Medizinische Universität Graz
- National Institutes of Health