Surfactant protein D is proatherogenic in mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 290; no. 6; pp. H2286 - H2294
• Main Authors: Sorensen, Grith L, Madsen, Jens, Kejling, Karin, Tornoe, Ida, Nielsen, Ole, Townsend, Paul, Poulain, Francis, Nielsen, Claus H, Reid, Kenneth B. M, Hawgood, Samuel, Falk, Erling, Holmskov, Uffe
• Format: Journal Article
• Language: English
• Published: United States 01.06.2006
• Subjects: Animals; Animals, Newborn; Aorta - pathology; Atherosclerosis - chemically induced; Atherosclerosis - metabolism; Atherosclerosis - pathology; Blotting, Western; Cells, Cultured; Cytokines - biosynthesis; Dietary Fats - pharmacology; Half-Life; Humans; Immunohistochemistry; Inflammation - pathology; Lipid Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium - pathology; Pulmonary Surfactant-Associated Protein D - genetics; Pulmonary Surfactant-Associated Protein D - isolation & purification; Pulmonary Surfactant-Associated Protein D - toxicity; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01105.2005

1 Medical Biotechnological Center, University of Southern Denmark, and 2 Department of Pathology, Odense University Hospital, Odense, Denmark; 3 Department of Biochemistry, Medical Research Council Immunochemistry Unit, University of Oxford, Oxford, United Kingdom; 4 Department of Pediatrics, University of California, Davis, California; 5 Copenhagen Blood Transfusion Centre, Copenhagen University Hospital, Copenhagen, Denmark; 6 Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, California; and 7 Department of Cardiology, Aarhus University Hospital (Skejby), Aarhus, Denmark Submitted 19 October 2005 ; accepted in final form 23 December 2005 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- 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. atherosclerosis; experimental animals; high-density lipoprotein; tumor necrosis factor- Address for reprint requests and other correspondence: U. Holmskov, Univ. of Southern Denmark, Medical Biotechnology Center, Winsloewparken 25,3, 5000 Odense C, Denmark (e-mail: uholmskov{at}health.sdu.dk )