Surfactant protein D is proatherogenic in mice.
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-alpha 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.
Sorensen
Grith L
GL
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25,3, 5000 Odense C, Denmark.
Madsen
Jens
J
Kejling
Karin
K
Tornoe
Ida
I
Nielsen
Ole
O
Townsend
Paul
P
Poulain
Francis
F
Nielsen
Claus H
CH
Reid
Kenneth B M
KB
Hawgood
Samuel
S
Falk
Erling
E
Holmskov
Uffe
U
D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004041:Dietary Fats / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004041:Dietary Fats; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha; D012313:RNA