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Abstract: FR-PO334

Macrophage Myeloperoxidase Deficiency Attenuates CKD Accelerated Atherosclerosis

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Mathew, Anna Vachaparampil, University of Michigan, Ann Arbor, Michigan, United States
  • Zeng, Lixia, University of Michigan, Ann Arbor, Michigan, United States
  • Cheofor, Vetalise Konje, University of Michigan, Ann Arbor, Michigan, United States
  • Roeser, Nancy F., University of Michigan, Ann Arbor, Michigan, United States
  • Byun, Jaeman, University of Michigan, Ann Arbor, Michigan, United States
  • Pennathur, Subramaniam, University of Michigan, Ann Arbor, Michigan, United States
Background

Increased myeloperoxidase (MPO) expression and activity are associated with cardiovascular disease in chronic kidney disease (CKD). We recently demonstrated the presence and catalytic activity of myeloperoxidase in vascular lesions of CKD mice. However, it is not known if modulation of MPO alters development and progression of exaggerated atherosclerosis in CKD.

Methods

Male and female LDL receptor-deficient mice were subjected to sham or 5/6 nephrectomy surgery (CKD). These mice were then irradiated and transplanted with bone marrow from MPO knock-out (MPOKO) mice to induce macrophage MPO deficiency. The mice were then maintained on a high-fat diet for 16 weeks. The extent of atherosclerosis was then assessed with oil red O staining of en face aortic sections.

Results

As anticipated, the CKD mice had significantly higher plasma creatinine, lower hematocrit, and decreased body weight when compared to the sham animals within the same group. After radiation, the MPOKO mice have decreased hematocrit and body weight but did not have any change in renal function compared to non-irradiated mice. Quantification of aortic oil red O stained lesional area revealed that CKD MPOKO mice had significantly decreased aortic plaque area compared to CKD mice with normal MPO expression. Both sham mice and CKD mice with MPOKO marrow showed decreased atherosclerosis compared to their wildtype counterparts and had no significant change in atherosclerosis when compared with each other.

Conclusion

Our studies demonstrate attenuation of atherosclerosis with macrophage MPO deficiency in CKD mouse model of atherosclerosis. These results strongly implicate macrophage-derived MPO in the pathogenesis of CKD accelerated atherosclerosis.

Funding

  • NIDDK Support