Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia

Felicia Antohe, Luminita Radulescu, Elena Puchianu, Michael D. Kennedy, Philip S. Low, Maya Simionescu

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

In the pathogenesis of atherosclerosis, macrophages become activated and play a crucial role in plaque formation. Activated synovial macrophages have recently been shown to express receptors for folic acid. We have determined whether activated macrophages also over-express folate receptor (FR) in atherosclerosis. Most normal cells express little or no FR, and, if FR is present on activated macrophages, folate-linked compounds and drugs could be selectively targeted to those cells that do express FR. To evaluate the FR on macrophages of atherosclerotic animals, golden Syrian hamsters were maintained on a hyperlipidemic diet until extensive vascular lesions had developed. Uptake of folic acid conjugated to fluorescent tags was then examined in tissue fragments from lesion-prone areas, and peritoneal activated macrophages were harvested from the same animals. Spectrofluorimetric and fluorescence microscopic analyses showed a significantly greater uptake of folate-conjugates by peritoneal macrophages of hyperlipidemic hamsters compared with those of hamsters fed a normal or folate-deficient diet. Systemically administered folate-fluorescent conjugates were found to accumulate as bright spots in protrusions of atherosclerotic plaques populated by macrophages, whereas a low level of fluorescence was detected uniformly dispersed across the lesion. The uptake of the folate conjugate by U937 macrophage cells grown in a high-lipid culture medium was significantly higher than in controls. Our data thus indicate that hyperlipidemic conditions induce an increased uptake of folate attributable to the over-expression of FRs on activated macrophages. This increase in FR expression can be exploited to deliver folate-linked compounds selectively to atherosclerotic lesions.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalCell and Tissue Research
Volume320
Issue number2
DOIs
StatePublished - May 2005

Keywords

  • Atherosclerosis
  • Folate receptor
  • Folic acid
  • Golden Syrian hamster
  • Hyperlipemia
  • Macrophages
  • Mouse (RAP)

ASJC Scopus subject areas

  • Anatomy
  • Clinical Biochemistry
  • Cell Biology

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