Transcriptional landscape of pulmonary artery endothelium reveals subpopulation- and disease-specific remodeling signatures

Communications Biology · 2026-05-11

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.

Lung transplant for CF: Low lung bacterial burden and immune mediators in year one associate with CLAD development

Journal of Cystic Fibrosis · 2025-10-10

Assessment of Post-Transplant Lung Function Alterations Using Free-Breathing Hyperpolarized Xenon MRI

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

Motivation: CLAD is the leading cause of long-term mortality in lung transplant (LTX) recipients, often diagnosed only after irreversible lung damage has occurred. Goal(s): To evaluate the effectiveness of dynamic Hyperpolarized Xenon-129 MRI in detecting early gas exchange abnormalities post LTX. Approach: We imaged lung transplant recipients, healthy controls, and COPD patients using dynamic HP-Xe MRI during free-breathing. Results: LTX recipients showed gradual declines and loss of gravitational gradients of the DP/GP over time, indicating impaired gas exchange even when appearing healthy. CLAD patients exhibited increased intraregional heterogeneity and diminished gravitational gradients, similar to patients with emphysema. Impact: The findings suggest that dynamic HP-Xe MRI is a sensitive tool for detecting early pulmonary function alterations in lung transplant recipients that traditional imaging methods might miss. This could enable earlier diagnosis and intervention of CLAD, potentially improving long-term survival.

Current intraoperative mechanical circulatory support strategies for bilateral lung transplantation surgery

JTCVS Techniques · 2025-03-31 · 3 citations

Objective: To discuss technical strategies and considerations to facilitate intraoperative extracorporeal membrane oxygenation (ECMO) management during lung transplantation. Methods: We review our institutional approach to the management of intraoperative ECMO during bilateral lung transplantation. Our proposed algorithm summarizes technical considerations based on the mechanical circulatory support (MCS) platform encountered in the operating room. Results: For patients without preoperative ECMO, an assessment of indications and available configurations in anticipation of the need for intraoperative ECMO is required. Our initial MCS approach for isolated respiratory failure is venovenous (VV) ECMO. If patients have pulmonary hypertension or right ventricular dysfunction with acceptable vascular access, then peripheral venoarterial (VA) ECMO is attempted. However, we maintain a low threshold for conversion to central aortic cannulation with a modified Seldinger technique through a clamshell or bilateral anterior thoracotomy incision. For patients bridged to lung transplantation on VV ECMO or venopulmonary (VPa) ECMO, our initial approach is to reverse flow through existing venous cannulas when possible and provide outflow through central aortic cannulation. Finally, for patients bridged to lung transplantation on peripheral VA ECMO, conversion to a central VA ECMO platform is preferred in the setting of poor flow or central hypoxemia. Importantly, all patients at our institution requiring MCS during lung transplantation are supported on a modified circuit that allows for rapid conversion from VA ECMO to full cardiopulmonary bypass (CPB) as needed. Conclusions: We propose a simple and technically feasible algorithm to facilitate the intraoperative conversion of VV, VPa, and VA ECMO patients to a modified central VA ECMO/CPB platform during bilateral lung transplantation.

ELEVATED LEVELS OF TROPONIN I DURING PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA ARE NOT PREDICTIVE OF CORONARY OBSTRUCTION

European Heart Journal Supplements · 2025-05-01

Abstract Introduction Supraventricular tachycardia (SVT), perceived by the patient (pt) as a feeling of palpitations and chest pain, is often associated with repolarization alterations (ST segment depression) that may suggest, together with the symptom “chest pain“, the co–presence of cardiac ischemia. However, the relationship between such alterations and the actual presence of cardiac ischemia is poor. Therefore, the ESC guidelines on chronic coronary syndromes recommend not taking into account such repolarization alterations (class III). Our case highlights how, not only the repolarization alterations, but also the increase in troponin, even if elevated, is of very little use in predicting the co–presence of ischemic heart disease in this contest. Clinical case A 56–year–old woman arrives in the Emergency Department (ED) for palpitations and chest pain. In her anamnesis she presents acquired post–surgical hypothyroidism (thyroid removal in 2005 for differentiated thyroid carcinoma) in replacement therapy (currently in euthyroidism). She also reports, for about 20 years, brief episodes of palpitations and shows a Holter EKG from 2023 in which sporadic supraventricular ectopic beats and a brief SVT are highlighted. No known cardiovascular risk factors are highlighted. On the EKG: SVT at 195 b/min with marked ST segment depression (Figure 1). Systolic blood pressure 70 mmHg. Vagal maneuvers ineffective. Adenosine 6 mg is administered ineffective and then 12 mg which allow the restoration of sinus rhythm. During observation in the ER, a significant increase in troponin I is observed 52.5 ng/L –› 3433 –› 3775 –› 1460 with a bell–shaped trend. Substantial normality of the other blood tests and Echocardiography. Despite the patient‘s asymptomatic nature, given the significant increase in troponin, it was decided to hospitalize her in cardiology and perform a coronary angiography which showed healthy coronary arteries (Figure 2). After 2 days from presentation in the ER, the patient was discharged on bisoprolol therapy and with an outpatient re–evaluation program. Conclusions The usefulness of measuring troponin during SVT is at least questionable and should be strongly limited. Even a high increase in troponin during SVT should not be considered a sign of ischemic heart disease and should not be used as a criterion for deciding whether or not to hospitalize the patient.Figure 1 Figure 2

One Year Weight Change and Survival After Lung Transplantation: A Lung Transplant Outcomes Group (LTOG) Study

The Journal of Heart and Lung Transplantation · 2025-04-01

Post-Operative Acute Kidney Injury Hazard Increases Across Typical Therapeutic Tacrolimus Target Levels: A Multicenter Lung Transplant Cohort Study

The Journal of Heart and Lung Transplantation · 2025-04-01

Extracellular Matrix and Fibroblast Activation in Lymphangioleiomyomatosis

American Journal of Respiratory Cell and Molecular Biology · 2025-09-08

Lymphangioleiomyomatosis (LAM) is a rare lung disease caused by hyperactivation of the mTORC1 (mechanistic/mammalian target of rapamycin 1) growth pathway in a subset of mesenchymal lung cells. Histopathologically, LAM lesions have been described as immature smooth muscle-like cells that are positive for the immature melanocytic marker HMB45/PMEL/gp100 and phosphorylated ribosomal protein S6 (pS6). Advances in single-cell sequencing technology allowed us to group LAM cells according to their expression of cancer stem cell (CSC) genes and identify three clusters: a high CSC-like state (i.e., stem-like state), an intermediate state, and a low CSC-like inflammatory state. We show here that, in unique LAM cells, many extracellular matrix (ECM) genes, including collagens and CTHRC1 (collagen triple helix repeat-containing 1), are expressed in the high and intermediate CSC-like LAM clusters and suggest that, as is observed in CSCs, the ECM may provide a shield for LAM lesions against immunosurveillance. In LAM-associated fibroblasts, the bisteric mTORC1-selective inhibitor RMC-5552 blocked translation of TGF-β (transforming growth factor-β)-induced COL1A1, COL6A1, and phosphorylation of the mTORC1 substrates ribosomal protein S6K1/S6 (S6K1/ribosomal protein S6) and 4E-BP1/eIF4E (eukaryotic initiation factor 4E-binding protein/translation initiation factor 4E), whereas rapamycin, the U.S. Food and Drug Administration-approved therapy for LAM disease, inhibited only the S6K1/S6 axis. C82, a Wnt/β-catenin transcription inhibitor, prevented TGF-β-induced collagens but not pS6 or p4E-BP1. This demonstrates that mTORC1-driven 4E-BP1/eIF4E rapamycin-insensitive translational control overrides transcriptional control of ECM genes. Inhibition by RMC-5552 of ECM and fibroblast activation may result in destruction of CSC-like LAM cells and provide more enduring therapy for LAM.

Perioperative Complications of Lung Transplant Have Time Differential Effects on Survival

The Journal of Heart and Lung Transplantation · 2025-04-01

The Lung Transplant Consortium (LTC) Promise Lung Study: Collecting Data to Guide Best Practices

The Journal of Heart and Lung Transplantation · 2025-04-01 · 1 citations