Publications by authors named "A J Brownstein"
Background: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.
Methods: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.
Results: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated , coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH.
Dissecting the lung transcriptome of pulmonary fibrosis-associated pulmonary hypertension.
Am J Physiol Lung Cell Mol Physiol
October 2024
Integrative multiomics can help elucidate the pathophysiology of pulmonary fibrosis (PF)-associated pulmonary hypertension (PH) (PF-PH). Weighted gene coexpression network analysis (WGCNA) was performed on a transcriptomic dataset of explanted lung tissue from 116 patients with PF. Patients were stratified by pulmonary vascular resistance (PVR), and differential gene expression analysis was conducted.
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- A study examined the connection between erythropoietic abnormalities and pulmonary arterial hypertension (PAH), finding that these issues are common in PAH patients and linked to more severe disease.
- The research involved 67 PAH patients and analyzed various blood parameters, discovering that immature reticulocyte fraction (IRF) positively correlates with worse hemodynamic measures, like mean pulmonary artery pressure, while negatively impacting cardiac output.
- IRF emerges as a significant biomarker for assessing the severity of PAH, tied to both erythropoiesis and iron metabolism challenges in patients.