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Abstract: SA-PO761

Circulating Monocytes From Patients With Primary Aldosteronism Display Exhaustion on Lipopolysaccharide Stimulation

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Kantauskaite, Marta, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Duvnjak, Blanka, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Schmidt, Claudia, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Srugies, Fabian, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Kolb, Thilo, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Koenigshausen, Eva, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Rump, Lars C., Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
  • Stegbauer, Johannes, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
Background

Aldosterone excess present in primary aldosteronism (PA) plays a critical role in the development of endothelial dysfunction, oxidative stress and chronic inflammation, which contributes to aggravated hypertensive organ damage. According to animal studies, aldosterone-induced immune cell activation directly contributes to vascular injury. As the monocytes are the main immune cells interacting with vascular wall during the injury, we proposed that patients with PA would demonstrate activated monocytes.

Methods

Monocytes from patients (N=9) before and 3 months after the treatment (N=9) and healthy individuals (N=6) were seeded into 96-well plates at 200000 cell/well in RPMI 1640 Dutch-modified culture medium (PAN Biotech) with supplements. After 4 hour rest time the cells were exposed to 10 ng/ml Lipopolysaccharides (LPS) O111:B4 from E.coli for 24 hours. After the incubation supernatants were collected for cytokine, chemokine and growth factor measurements using Bio-Plex Pro Human Cytokine 17-plex Assay. Clinical and laboratory data were collected from patients records.

Results

Before the treatment PA patients displayed significantly higher concentrations of following cytokines and growth factors than healthy controls: G-CSF, IFN-γ, TNF-α, IL-6, IL-10, IL-8, IL-17, MCP-1. Moreover, before the treatment Aldosterone-Renin-Quotient (ARQ) correlated positively with IL-6 (r 0.667, p=0.05) and MCP-1(r 0.883, p=0.002). After the treatment was initiated, we have observed normalized blood pressure (median 139/85mmHg vs 130/80mmHg, p<0.05) and significantly lower ARQ (83 (59 – 261) vs 13(3.6 -9.4), p<0.05). In addition, cytokine levels in monocyte supernatants normalized and reached levels similar to healthy controls. Upon the stimulation with LPS, PA patients demonstrated a blunted immune response whereas the treatment restored the cytokine response upon LPS stimulation. Moreover, lower IL-6 (r -0.766, p=0.27), TNF-α (r -0.802, p=0.017) and G-CSF (r -0.719, p = 0.045) concentration upon LPS stimulation was associated with higher diastolic blood pressure.

Conclusion

Patients with primary aldosteronism demonstrate higher cytokine levels at a steady state and a type of reversible endoxin tolerance upon stimulation which might contribute to the increase in blood pressure.

Funding

  • Government Support – Non-U.S.