Association of attenuated leptin signaling pathways with impaired cardiac function under prolonged high-altitude hypoxia.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Leptin*/metabolism ; Leptin*/blood ; Signal Transduction* ; Altitude* ; Hypoxia*/metabolism ; Hypoxia*/physiopathology; Animals ; Rats ; Male ; Humans ; Altitude Sickness/metabolism ; Altitude Sickness/physiopathology ; Myocardium/metabolism ; Myocardium/pathology ; Adult ; Heart/physiopathology
    • Abstract:
      Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na + /K + transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.
      (© 2024. The Author(s).)
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    • Grant Information:
      3332022143 Fundamental Research Funds for the Central Universities; 2021-I2M-1-022 CAMS Innovation Fund for Medical Sciences
    • Contributed Indexing:
      Keywords: Antarctica; Cardiovascular diseases; Humans; Hypoxia; Leptin; Rats
    • Accession Number:
      0 (Leptin)
    • Publication Date:
      Date Created: 20240503 Date Completed: 20240503 Latest Revision: 20240523
    • Publication Date:
      20240523
    • Accession Number:
      PMC11068766
    • Accession Number:
      10.1038/s41598-024-59559-6
    • Accession Number:
      38702334