The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia.

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  • Additional Information
    • Source:
      Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8904841 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2796 (Electronic) Linking ISSN: 09546820 NLM ISO Abbreviation: J Intern Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Blackwell Scientific Publications, c1989-
    • Subject Terms:
      Diabetes Mellitus, Type 2* ; Hyperlipoproteinemia Type II*/complications; Animals ; Rats ; Cholesterol, LDL ; Reactive Oxygen Species/metabolism ; Erythrocytes/metabolism
    • Abstract:
      Background: Patients with familial hypercholesterolemia (FH) display high levels of low-density lipoprotein cholesterol (LDL-c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS).
      Objective: To test the hypothesis that RBCs from patients with FH (FH-RBCs) and elevated LDL-c induce endothelial dysfunction.
      Methods and Results: FH-RBCs and LDL-c >5.0 mM induced endothelial dysfunction following 18-h incubation with isolated aortic rings from healthy rats compared to FH-RBCs and LDL-c <2.5 mM or RBCs from healthy subjects (H-RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH-RBCs and LDL-c >5.0 mM. A superoxide scavenger, present throughout the 18-h incubation, attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. ROS production was elevated in these RBCs in comparison with H-RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4-hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups.
      Conclusion: FH-RBCs induce endothelial dysfunction dependent on LDL-c levels via arginase 1 and ROS-dependent mechanisms.
      (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)
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    • Contributed Indexing:
      Keywords: arginase; endothelial dysfunction; familial hypercholesterolemia; low-density lipoprotein; reactive oxygen species; red blood cell
    • Accession Number:
      0 (Cholesterol, LDL)
      0 (Reactive Oxygen Species)
    • Publication Date:
      Date Created: 20221103 Date Completed: 20230104 Latest Revision: 20230415
    • Publication Date:
      20230415
    • Accession Number:
      PMC10092865
    • Accession Number:
      10.1111/joim.13580
    • Accession Number:
      36324273