Renal dysfunction potentiates foam cell formation by repressing ABCA1

Yiqin Zuo, Patricia Yancey, Iris Castro, Wasif Khan, Masaru Motojima, Iekuni Ichikawa, Agnes B. Fogo, MacRae F. Linton, Sergio Fazio, Valentina Kon

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

OBJECTIVE-: Patients with chronic kidney disease (CKD) have the highest risk for atherosclerotic cardiovascular disease (CVD). Current interventions have been insufficiently effective in lessening excess incidence and mortality from CVD in CKD patients versus other high-risk groups. The mechanisms underlying the heightened risk remain obscure but may relate to differences in CKD-induced atherogenesis, including perturbation of macrophage cholesterol trafficking. METHODS AND RESULTS-: We examined the impact of renal dysfunction on macrophage cholesterol homeostasis in the apoE mouse model of atherosclerosis. Renal impairment induced by uninephrectomy dramatically increased macrophage cholesterol content, linked to striking impairment of macrophage cholesterol efflux. This blunted efflux was associated with downregulation of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) and activation of the nuclear factor-kappa B (NF-κB). Treatment with the angiotensin receptor blocker (ARB) losartan decreased NF-κB and restored cholesterol efflux. CONCLUSIONS-: Our findings show that mild renal dysfunction perturbs macrophage lipid homeostasis by inhibiting cholesterol efflux, mediated by decreased ABCA1 transporter and activation of NF-κB, and that ARB can restore cholesterol efflux.

Original languageEnglish (US)
Pages (from-to)1277-1282
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Keywords

  • Angiotensin
  • Atherosclerosis
  • ATP-binding cassette transporter A1
  • Macrophage
  • Renal impairment

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Zuo, Y., Yancey, P., Castro, I., Khan, W., Motojima, M., Ichikawa, I., Fogo, A. B., Linton, M. F., Fazio, S., & Kon, V. (2009). Renal dysfunction potentiates foam cell formation by repressing ABCA1. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(9), 1277-1282. https://doi.org/10.1161/ATVBAHA.109.188995