Atherosclerosis in chronic kidney disease: The role of macrophages

Valentina Kon, MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe g-/g- mice are enriched in cholesterol owing to downregulation of cholesterol transporter ATP-binding cassette subfamily A member 1 levels and activation of nuclear factor κB, which leads to impaired cholesterol efflux. Interestingly, treatment with an angiotensin-II-receptor blocker (ARB) improves these effects. Moreover, atherosclerotic aortas from Apoe g-/g- mice transplanted into renal-ablated normocholesterolemic recipients show plaque progression and increased macrophage content instead of the substantial regression seen in recipient mice with intact kidneys. ARBs reduce atherosclerosis development in mice with partial renal ablation. These results, combined with the clinical benefits of angiotensin-converting-enzyme (ACE) inhibitors and ARBs in patients with CKD, suggest an important role for the angiotensin system in the enhanced susceptibility to atherosclerosis seen across the spectrum of CKD. The role of macrophages could explain why these therapies may be effective in end-stage renal disease, one of the few conditions in which statins show no clinical benefit.

Original languageEnglish (US)
Pages (from-to)45-54
Number of pages10
JournalNature Reviews Nephrology
Volume7
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Chronic Renal Insufficiency
Atherosclerosis
Macrophages
Cholesterol
Kidney
Apolipoproteins E
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Arteritis
ATP-Binding Cassette Transporters
Angiotensin Receptor Antagonists
Angiotensins
Angiotensin-Converting Enzyme Inhibitors
Chronic Kidney Failure
Aorta
Creatinine
Cardiovascular Diseases
Down-Regulation
Animal Models
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Atherosclerosis in chronic kidney disease : The role of macrophages. / Kon, Valentina; Linton, MacRae F.; Fazio, Sergio.

In: Nature Reviews Nephrology, Vol. 7, No. 1, 01.2011, p. 45-54.

Research output: Contribution to journalArticle

Kon, Valentina ; Linton, MacRae F. ; Fazio, Sergio. / Atherosclerosis in chronic kidney disease : The role of macrophages. In: Nature Reviews Nephrology. 2011 ; Vol. 7, No. 1. pp. 45-54.
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