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Abstract: TH-PO526

Increases in Circulating Granulocyte Neutral Sphingomyelinase 2 Expression in Dialysis Patients Correlate Directly with the Propensity for Vascular Calcification

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Carrillo-Lopez, Natalia, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Ulloa, Catalina, Division of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain
  • Rodriguez-Carrio, Javier, Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Spain
  • Panizo, Sara, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Martinez-Arias, Laura, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Martin-Carro, Beatriz, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Martin-Virgala, Julia, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Rodriguez-Suarez, Carmen, Division of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain
  • Cannata-Andia, Jorge B., Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
  • Dusso, Adriana S., Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain
Background

Systemic inflammation is a risk factor for atherosclerosis and vascular calcification in the general population and in chronic kidney disease (CKD) patients. Because increases in neutral sphyngomyelinase 2 (nSMase2) are essential for the severity of age-induced inflammation in health and atherosclerosis in the ApoE null mouse and contribute to initiate medial calcification in uremia, this study evaluated whether leukocyte gene expression of nSMase2 and its inducer in the vasculature, TNFα, could estimate the propensity for vascular calcification.

Methods

Peripheral blood mononuclear cells (PBMC) and granulocytes, from 28 peritoneal dialysis (PD) patients and 16 normal adults, matched for age and gender, were obtained from fresh blood using Fycoll gradient. A lumbar X-ray measured Kauppila index (KI) to estimate subclinical (KI<5) or clinical (KI>5) risk for vascular calcification (VC).

Results

In adults older than 40 with normal renal function, PBMC TNFα mRNA levels correlated directly with age (r=0.61; p<0.05; n=10), a risk factor for vascular damage. Furthermore, PBMC TNFα increased by 52% in peritoneal dialysis patients (p<0.03) compared to controls and, similar to the vasculature, PBMC nSMase2 gene expression increased in parallel with the elevations in TNFα in both healthy adults (r=0.57; p<0.02; n=16) and PD patients (r=0.56; p<0.01; n=28). In circulating granulocytes, TNFα was also 2-fold higher in PD patients, but with levels 2.2-fold lower than those in PBMC, even in normal controls. Significantly, the increases in granulocyte nSMase2 correlated directly with KI>5 (r=0.65; p<0.05; n=11), a recognized biomarker of the clinical risk for vascular calcification, but not with TNFα.

Conclusion

While in PBMC, the higher TNFα mRNA levels correlating with increases in nSMase2 may estimate the degree of systemic inflammation, the increased granulocyte nSMase2 gene expression appear sufficient to reflect VC risk.

Funding

  • Government Support - Non-U.S.