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METALLOMICS PROFILE IN PULMONARY ARTERIAL HYPERTENSION PATIENTS

      TOPIC: Pulmonary Vascular Disease
      TYPE: Original Investigations
      PURPOSE: Exposure to nonessential metals has been linked to increased incidence of cardiovascular diseases. However, the relationship between metals and pulmonary arterial hypertension (PAH) is less investigated. We aimed to comprehensively analyze metallomics profiles in PAH patients to identify potential roles of nonessential metal toxicity and essential metal dyshomeostasis in the pathogenesis of PAH.
      METHODS: After IRB approval and informed consent, we recruited 20 PAH patients and 3 control subjects in this prospective observational study. Blood and urine samples were obtained for measuring 31 metals in whole-blood, plasma and urine samples using an X Series II quadrupole inductively coupled plasma mass spectrometry (ICP-MS). Metal concentrations were compared between control and PAH groups with two sample t-test for continuous variables. Statistical analysis is conducted using SAS 9.5 and results are declared significant at p<0.05.
      RESULTS: In the blood samples, PAH group showed 5 times higher cadmium concentration when compared to control group although not statistically significant (p=0.083). Interestingly, thorium concentration was significantly lower in the PAH group (p=0.006). For the plasma samples, PAH showed significantly higher sodium (p=0.034), lower manganese (p=0.006) and lower arsenic (p=0.02) levels. In the urine samples, PAH patients have increased levels of zinc (14 times, p=0.107), arsenic (6.24 times, p=0.484), and cadmium (11 times, p=0.173) relative to controls although not statistically significant. We then compared idiopathic PAH (n=6) and control (n=3) metal levels with the presumption that metal dyshomeostasis might play a larger role in idiopathic PAH. Less thorium in the blood (p=0.027); higher sodium (p=0.006, lower manganese (p=0.027) and lower arsenic (p=0.043) in the plasma; higher selenium (p=0.047) and molybdenum (p=0.019) in the urine were found in idiopathic PAH patients. Idiopathic PAH urine cadmium level was 18 times higher than controls although not statistically significant (p=0.091). We also found significant variations among all metals in urine, blood and plasma samples of PAH patients with large standard deviations indicating the heterogenicity of PAH pathogenesis.
      CONCLUSIONS: We performed comprehensive metallomics profiling for PAH patients. Thorium, sodium, manganese, arsenic, zinc, cadmium levels were abnormal in PAH patients compared to controls. In idiopathic PAH patients, selenium and molybdenum were elevated in addition to above mentioned abnormal metals in the entire PAH group.
      CLINICAL IMPLICATIONS: Identification of abnormal essential and non-essential metal levels in PAH patients might shed light on the need to prevent population exposure to environmental nonessential metals, maintain essential metal balances and provide novel therapeutic strategies with non-essential metal chelation and essential metal optimization for PAH patients.
      DISCLOSURES: No relevant relationships by Ozan Akca, source=Web Response
      No relevant relationships by Lu Cai, source=Web Response
      No relevant relationships by Oscar Chen, source=Web Response
      Speaker/Speaker's Bureau relationship with United therapeutics Please note: $5001 - $20000 by Karim El-Kersh, source=Web Response, value=Honoraria
      Removed 04/21/2021 by Karim El-Kersh, source=Web Response
      Advisory Committee Member relationship with United therapeutics Please note: $1001 - $5000 by Karim El-Kersh, source=Web Response, value=Consulting fee
      Removed 04/21/2021 by Karim El-Kersh, source=Web Response
      Advisory Committee Member relationship with Actelion Please note: $5001 - $20000 by Karim El-Kersh, source=Web Response, value=Consulting fee
      Removed 04/21/2021 by Karim El-Kersh, source=Web Response
      Advisory Committee Member relationship with United Therapeutics Please note: Current Added 04/23/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee
      Advisory Committee Member relationship with Actelion Please note: 2019 and 2020 Added 04/23/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee
      Speaker/Speaker's Bureau relationship with United Therapeutics Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria
      Advisory Committee Member relationship with United Therapeutics Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria
      Advisory Committee Member relationship with Actelion Please note: 2019 and 2020 Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Honoraria
      Consultant relationship with Acceleron Pharma Please note: Current Added 04/29/2021 by Karim El-Kersh, source=Web Response, value=Consulting fee
      No relevant relationships by C. Danielle Hopkins, source=Web Response
      Consultant relationship with GE Healthcare Please note: 2019-Present Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Consulting fee
      Research grant relationship with Gilead Sciences Please note: 2020-2022 Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Grant/Research Support
      Consultant relationship with GE Healthcare Please note: 2019 to Present Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Consulting fee
      Research Funding relationship with Gilead Sciences Please note: 2020-2022 Added 04/27/2021 by Jiapeng Huang, source=Web Response, value=Grant/Research Support
      No relevant relationships by Caitlin Wessel, source=Web Response