Metabolic reprogramming, oxidative stress, and pulmonary hypertension

Pokharel, Marissa D.; Marciano, David P.; Fu, Panfeng; Franco, María Clara; Unwalla, Hoshang; Tieu, Kim; Fineman, Jeffrey R.; Wang, Ting; Black, Stephen M.

doi:10.1016/j.redox.2023.102797

Cited by 35 publications

(10 citation statements)

References 232 publications

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“…Oxidative phosphorylation and HIF-1 signaling pathway were the top signi cantly regulated KEGG pathway identi ed in PAH group. Enrichment analyse of GSEA showed that oxidative phosphorylation were involved in PAH, those results was consistent with evidence that oxidative stress was critical in the pathophysiology of PAH, antioxidant treatment might be the potential therapeutic target for the treatment of PAH [23,24]. Of note, many similarities to human cancers in the pulmonary vasculature, up-regulated or down-regulated gene group also be of interest for PAH, including neutrophil activation involved in immune response, chemokine receptor activity, and calcium ion homeostasis had been implicated as the cause or consequence of PAH [25,26].…”

Section: Discussionsupporting

confidence: 80%

Integration of transcriptomics, proteomics, phosphoproteomics analysis for characterization of pulmonary arterial hypertension in Chinese people

liu,

Zhou,

Wang

et al. 2024

Preprint

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Background Pulmonary arterial hypertension (PAH), a fatal disease, is characterized by pulmonary vascular remodeling and vascular resistance. However, the molecular mechanisms underlying the pathogenesis of PAH remained to be incompletely understood. Methods RNA-seq, 4D Lable-free proteomics and phosphoproteomics were used to detect the levels of mRNA, proteins, and phosphoproteins in lung tissues from PAH patients, respectively. Parallel reaction monitoring (PRM) was carried out to verify the expression of the differentially expressed proteins. Results Totally, 967 differentially expressed genes (|log2FoldChange|>1 and p < 0.05), 764 differentially expressed proteins and 411 phosphoproteins were observed after data filtering (|log2FoldChange|>1 and p < 0.05) in lung tissues of PAH patients as compared with the control group. Integrated analysis of the three omic measures revealed that the biological processes involving inflammation, ion channel and metabolism were closely associated with PAH. Several signaling pathways, such as ferroptosis, HIF-1, PI3K-AKT, and Rap1 might be related to the development of PAH. Conclusions This study combined multi-omics characteristic profiling to find out the changed genes or proteins that contributed to a detailed pathogenic of PAH. It would have the benefit of looking for the novel and effective treatment targets and therapeutic drugs to PAH patients.

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Section: Discussionsupporting

confidence: 80%

Integration of transcriptomics, proteomics, phosphoproteomics analysis for characterization of pulmonary arterial hypertension in Chinese people

liu,

Zhou,

Wang

et al. 2024

Preprint

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“…Furthermore, proteomic analysis of PAECs revealed reduced expression levels of solute carrier family 25A1 (SLC25A1), a mitochondrial citrate transporter that facilitates the efflux of citrate from the mitochondria to the cytoplasm [ 86 ]. Through the inhibition of PDH, HIF-1α activation effectively impedes the conversion of pyruvate to acetyl-CoA, thereby obstructing the entry of pyruvate into the TCA cycle under hypoxic conditions [ 87 ]. These findings indicate that the dysregulated expression of metabolites and related genes in the TCA cycle in PH patients may reflect mitochondrial dysfunction in PH lung tissue.…”

Section: Research Progress On Other Metabolic Pathwaysmentioning

confidence: 99%

Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics

Ba,

Guo,

Jiang

et al. 2024

Respir Res

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Pulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of research progress, the absence of definitive curative therapies remains a critical challenge, leading to high mortality rates. Recent studies have shown that serious metabolic disorders generally exist in PH animal models and patients of PH, which may be the cause or results of the disease. It is imperative for future research to identify critical biomarkers of metabolic dysfunction in PH pathophysiology and to uncover metabolic targets that could enhance diagnostic and therapeutic strategies. Metabolomics offers a powerful tool for the comprehensive qualitative and quantitative analysis of metabolites within specific organisms or cells. On the basis of the findings of the metabolomics research on PH, this review summarizes the latest research progress on metabolic pathways involved in processes such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in the context of PH.

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“…Some have postulated that this glycolytic shift in PAECs allow these endothelial cells to use glucose for efficiently conferring a functional advantage over oxidative phosphorylation [ 33 ]. Moreover, endothelial cells are more resistant to hypoxia than other cell types because of preferential anaerobic glycolytic pathway particularly when glucose is readily available [ 33 , 36 ]. Contrastingly, when glucose levels are reduced, endothelial cells are more sensitive to hypoxic/low oxygen states, suggesting that glycolysis renders PAECs more resistant to hypoxia, and that hyperglycemia enhances this state of resistance.…”

Section: Metabolic Dysregulation In Pulmonary Hypertensionmentioning

confidence: 99%

“…Shared alterations in fatty acid oxidation are another commonality between PAH and DM, which has been observed in PAH cardiomyocytes [ 34 , 36 ]. Increased levels of carnitine and acylcarnitine in plasma from PAH patients, also support abnormal mitochondrial fatty acid oxidation [ 33 ].…”

Section: Metabolic Dysregulation In Pulmonary Hypertensionmentioning

confidence: 99%

Pulmonary Hypertension and Hyperglycemia—Not a Sweet Combination

Bruck,

Pandit

2024

Diagnostics

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Hyperglycemia and pulmonary hypertension (PH) share common pathological pathways that lead to vascular dysfunction and resultant cardiovascular complications. These shared pathologic pathways involve endothelial dysfunction, inflammation, oxidative stress, and hormonal imbalances. Individuals with hyperglycemia or pulmonary hypertension also possess shared clinical factors that contribute to increased morbidity from both diseases. This review aims to explore the relationship between PH and hyperglycemia, highlighting the mechanisms underlying their association and discussing the clinical implications. Understanding these common pathologic and clinical factors will enable early detection for those at-risk for complications from both diseases, paving the way for improved research and targeted therapeutics.

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Metabolic reprogramming, oxidative stress, and pulmonary hypertension

Cited by 35 publications

References 232 publications

Integration of transcriptomics, proteomics, phosphoproteomics analysis for characterization of pulmonary arterial hypertension in Chinese people

Integration of transcriptomics, proteomics, phosphoproteomics analysis for characterization of pulmonary arterial hypertension in Chinese people

Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics

Pulmonary Hypertension and Hyperglycemia—Not a Sweet Combination

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