American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2024
Digital Spatial Profiling Identifies Distinct Molecular Signatures of Vascular Lesions in Pulmonary Arterial Hypertension.
Rationale: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling caused by plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia. Objective: We sought to test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries. Methods: We used digital spatial transcriptomics to profile the genomewide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n = 11) and compared these data with the intima+media hypertrophy and adventitia of control pulmonary artery (n = 5). ⋯ Cellular deconvolution indicated variability in the number of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcript profiling. Conclusions: IPAH lesions express unique molecular transcript profiles enriched for pathways involving pathogenetic pathways, including genetic disease drivers, innate and acquired immunity, hypoxia sensing, and angiogenesis signaling. These data provide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and therapeutic targets in this highly morbid disease.
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Am. J. Respir. Crit. Care Med. · Aug 2024
Patent Ductus Arteriosus and Lung MRI Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.
Rationale: Hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. Objectives: To assess the associations between hsPDA duration and clinical outcomes, PH, and phenotypic differences on lung magnetic resonance imaging (MRI). ⋯ Measurements and Main Results: In total, 133 infants born at 26.2 ± 1.9 weeks, weighing 776 ± 276 g, were reviewed (47 with no hsPDA, 44 with hsPDA 1-60 days, and 42 with hsPDA >60 d). hsPDA duration > 60 days was associated with BPD severity (P < 0.01), PH at 36 weeks' PMA (adjusted odds ratio [aOR], 9.7 [95% confidence interval (CI), 3.3-28.4]), PH-PVD (aOR, 6.5 [95% CI, 2.3-18.3]), and tracheostomy or death (aOR, 3.0 [95% CI, 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (P = 0.03) and indexed total lung volume (P = 0.01) but not whole-lung hyperdensity (P = 0.91). Conclusions: In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.