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Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
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Atherosclerosis in chronic kidney disease: the role of macrophages

Valentina Kon1, MacRae F Linton, Sergio Fazio

  • 1Department of Pediatrics, Vanderbilt University Medical Center, 383 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37332-6300, USA.

Nature Reviews. Nephrology
|November 25, 2010
PubMed

Insights

Chronic kidney disease (CKD) promotes atherosclerosis by altering macrophage cholesterol metabolism. Angiotensin system blockers show promise in mitigating this increased cardiovascular risk in CKD patients.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Immunology

Background:

  • Patients with chronic kidney disease (CKD) exhibit a higher risk of atherosclerotic cardiovascular disease.
  • Macrophages play a critical role in atherogenesis by regulating arterial wall inflammation and cholesterol homeostasis.
  • CKD adversely affects macrophage function, promoting a proatherogenic state.

Purpose of the Study:

  • To investigate the impact of CKD on macrophage cholesterol metabolism and atherosclerosis.
  • To explore the role of the angiotensin system in CKD-associated atherosclerosis.
  • To evaluate the therapeutic potential of angiotensin-II-receptor blockers (ARBs) in mitigating atherosclerosis in CKD models.

Main Methods:

  • Utilized Apoe(-/-) mice, a model for atherosclerosis, with and without uninephrectomy or partial renal ablation.
  • Assessed macrophage cholesterol content, ATP-binding cassette subfamily A member 1 (ABCA1) levels, and nuclear factor κB (NF-κB) activation.
  • Employed aortic transplantation models to study plaque progression in renal-ablated recipients.
  • Administered angiotensin-II-receptor blockers (ARBs) to evaluate their effects on atherosclerosis.

Main Results:

  • Macrophages from uninephrectomized Apoe(-/-) mice showed impaired cholesterol efflux due to reduced ABCA1 levels and activated NF-κB.
  • Atherosclerotic aortas transplanted into renal-ablated mice exhibited plaque progression, unlike in intact kidney recipients.
  • ARBs treatment improved cholesterol handling in macrophages and reduced atherosclerosis development in mice with partial renal ablation.

Conclusions:

  • The angiotensin system plays a significant role in the heightened susceptibility to atherosclerosis observed across the spectrum of CKD.
  • Altered macrophage function, particularly impaired cholesterol efflux, contributes to CKD-associated atherosclerosis.
  • Therapies targeting the angiotensin system may offer a beneficial strategy for managing cardiovascular complications in CKD patients, including those with end-stage renal disease.

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