Reduced Apela/APJ system expression in patients with pulmonary artery hypertension secondary to chronic obstructive pulmonary disease

Hu, Yuexin; Zong, Yani; Jin, Liangli; Zou, Jue; Wang, Zhi

doi:10.1016/j.hrtlng.2023.01.008

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…Consistently, APELA was downregulated in small airways of patients with COPD. Similar results have been reported to decrease apelin in patients with pulmonary artery hypertension secondary to COPD ( 52 ). Apelin plays protective role in obesity, by regulating the inflammation and oxidative stress ( 53 ).…”

Section: Discussionsupporting

confidence: 90%

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Zhang,

Qin,

Zhou

et al. 2023

Front. Endocrinol.

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BackgroundObesity and chronic obstructive pulmonary disease (COPD) are prevailing worldwide, bringing a heavy medical burden. Clinical and pathophysiological relationship between obesity and COPD is paradoxical and elusive. We aim to explore their inherent associations from clinical, genetic, and animal levels.MethodsWe performed literature review and cohort analysis of patients with COPD to compare lung function, symptom, and prognosis among different weight groups. After retrieving datasets of obesity and COPD in Gene Expression Omnibus (GEO) database, we carried out differentially expressed gene analysis, functional enrichment, protein–protein interactions network, and weighted gene co-expression network analysis. Then, we acquired paraffin-embedded lung tissues of fatty acid–binding protein 4–Cre-BMPR2fl/fl conditional knockout (CKO) mice that were characterized by adipocyte-specific knockout of bone morphogenetic protein receptor 2 (BMPR2) for staining and analysis.ResultsOur cohort study reports the effect of obesity on COPD is inconsistent with previous clinical studies. Lung function of overweight group was statistically superior to that of other groups. We also found that the inflammatory factors were significantly increased hub genes, and cytokine-associated pathways were enriched in white adipose tissue of patients with obesity. Similarly, injury repair–associated genes and pathways were further enhanced in the small airways of patients with COPD. CKO mice spontaneously developed lung injury, emphysema, and pulmonary vascular remodeling, along with increased infiltration of macrophages. BMPR2-defiecient adipocytes had dysregulated expression of adipocytokines.ConclusionInflammation and abnormal repair might be potential mechanisms of the pathological association between obesity and COPD. BMPR2-associated adipocyte dysfunction promoted lung inflammation and aberrant repair, in which adipocytokines might play a role and thus could be a promising therapeutic target.

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Section: Discussionsupporting

confidence: 90%

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Zhang,

Qin,

Zhou

et al. 2023

Front. Endocrinol.

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Therapeutic potential of apelin and Elabela in cardiovascular disease

Gao

Chen

2023

Biomedicine & Pharmacotherapy

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Pharmacokinetics, Mass Balance, Tissue Distribution and Metabolism of [14C]101BHG-D01, a Novel Muscarinic Receptor Antagonist, in Rats

Gao,

Yang,

et al. 2023

CDM

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Background:: 101BHG-D01, a novel long-acting and selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD), is undergoing Phase Ib clinical trial in patients and has shown its potential efficacy. Its preparation method and medical use thereof have been patented in the United States (Patent No.US9751875B2). Objective:: In this study, the pharmacokinetics, mass balance, tissue distribution and metabolism of radioactive 101BHG-D01 were investigated in rats after an intravenous dose of 1 mg/kg [14C]101BHG-D01 (100 μCi/kg). Methods:: Radioactivity in rat plasma, urine, feces, and tissues was measured by liquid scintillation counting (LSC), and metabolite profiling and identification were conducted by UHPLC-β-RAM and UHPLC-Q-Exactive Plus MS. Results:: The total radioactivity of the study drug in rat plasma rapidly declined with an average terminal elimination half-life of 0.35 h. The radioactivity in most tissues reached the maximum concentration at 0.25 h post-- dosing. The radioactivity mainly concentrated in the kidney and pancreas. The drug-related substances tended to be distributed into the blood cells in the circulation. At 168 h post dosing, the mean recovery of the total radioactivity in urine and feces was 78.82%. Fecal excretion was the major excretion route, accounting for approximately 61% of the radioactive dose. The study drug was metabolized extensively, and a total of 17 metabolites were identified in rat plasma, urine, and feces. The major metabolic pathways involved oxidation, oxidation and dehydrogenation, and O-dephenylation. Conclusion:: In conclusion, the study results are useful for better understanding the pharmacokinetic profiles of 101BHG-D01 and provide a robust foundation for subsequent clinical studies.

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Reduced Apela/APJ system expression in patients with pulmonary artery hypertension secondary to chronic obstructive pulmonary disease

Cited by 3 publications

References 33 publications

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD

Therapeutic potential of apelin and Elabela in cardiovascular disease

Pharmacokinetics, Mass Balance, Tissue Distribution and Metabolism of [14C]101BHG-D01, a Novel Muscarinic Receptor Antagonist, in Rats

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