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Cell and Tissue Research

, Volume 336, Issue 2, pp 237–248 | Cite as

Effect of depletion of monocytes/macrophages on early aortic valve lesion in experimental hyperlipidemia

  • Manuela Voinea Calin
  • Ileana Manduteanu
  • Elena Dragomir
  • Emanuel Dragan
  • Manuela Nicolae
  • Ana Maria Gan
  • Maya Simionescu
Regular Article

Abstract

Monocytes/macrophages are key players throughout atheroma development. The aim of this study was to determine the role of macrophages in lesion formation in heart valves in hyperlipidemia. We examined whether systemic depletion of monocytes/macrophages had a beneficial or adverse effect on the development of lesions in hyperlipemic hamsters injected twice weekly (for 2 months) with clodronate-encapsulated liposomes (H+Lclod), a treatment that selectively induces significant monocyte apoptosis. Hyperlipemic hamsters were employed as controls, as were hyperlipemic hamsters treated with plain liposomes. We assayed serum cholesterol (CH) and triglycerides (TG), the lipid and collagen contents and the size of the valve lesions, the matrix metalloproteinases (MMPs) in the serum and vessel wall, apolipoprotein E (ApoE), interleukin-1β (IL-1β), and superoxide anion production. In comparison with controls, H+Lclod hamsters exhibited: (1) increased lipid and collagen accumulation within the lesions, (2) decreased activity of MMP-9 and MMP-2 in sera and aortic homogenates, (3) decreased serum CH and TG and decreased expression of ApoE in sera and liver, (4) reduced expression of IL-1β in aorta and liver homogenates, and (5) no change in the level of superoxide anion in the aorta. Thus, initially, the presence of the macrophages is beneficial in valvular lesion formation. Depletion of monocytes/macrophages is a two-edged sword having a beneficial effect by decreasing the expression of IL-1β and MMP activities but an adverse effect by inducing a significant increase in the lipid and collagen content and expansion of valvular lesions.

Keywords

Aortic valve Atherosclerosis Liposomes Clodronate Macrophages Hamster (Golden Syrian) 

Notes

Acknowledgments

The authors are indebted to Gabriela Mesca, Rodica Tatia, Ana Manole, Safta Nae, Nicoleta Dobre, and Marilena Daju for technical assistance and to Dr. Adrian Manea for help with the determination of the superoxide anion.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Manuela Voinea Calin
    • 1
  • Ileana Manduteanu
    • 1
  • Elena Dragomir
    • 1
  • Emanuel Dragan
    • 1
  • Manuela Nicolae
    • 1
  • Ana Maria Gan
    • 1
  • Maya Simionescu
    • 1
  1. 1.Institute of Cellular Biology and Pathology “Nicolae Simionescu”BucharestRomania

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