Surfactant protein D is proatherogenic in mice

Grith L. Sorensen, Jens Madsen, Karin Kejling, Ida Tornoe, Ole Nielsen, Paul Townsend, Francis R Poulain, Claus H. Nielsen, Kenneth B M Reid, Samuel Hawgood, Erling Falk, Uffe Holmskov

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF-α was reduced in Spd-/- mice (45% difference). SP-D was proatherogenic in the mouse model used. The effect is likely to be due to the observed disturbances of plasma lipid metabolism and alteration of the inflammatory process, which underlie the reduced susceptibility to atherosclerosis in Spd-/- mice.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Atherosclerosis
  • Experimental animals
  • High-density lipoprotein
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology

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  • Cite this

    Sorensen, G. L., Madsen, J., Kejling, K., Tornoe, I., Nielsen, O., Townsend, P., Poulain, F. R., Nielsen, C. H., Reid, K. B. M., Hawgood, S., Falk, E., & Holmskov, U. (2006). Surfactant protein D is proatherogenic in mice. American Journal of Physiology - Heart and Circulatory Physiology, 290(6). https://doi.org/10.1152/ajpheart.01105.2005