Atherosclerosis in chronic kidney disease: The role of macrophages

Valentina Kon, MacRae F. Linton, Sergio Fazio

    Research output: Contribution to journalReview article

    31 Scopus citations

    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 1 2011

    ASJC Scopus subject areas

    • Nephrology

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