Abstract
BACKGROUND: Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease.
METHODS AND RESULTS: Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa-/-) were crossed to Ldlr-/- mice (Saa-/-Ldlr-/-). Saa-/-Ldlr-/- mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate artery after consuming a high-fat, high-cholesterol Western-type diet for 6 weeks. The lesions were predominantly macrophage foam cells. The phenotype was lost in more mature lesions in mice fed a Western-type diet for 12 weeks, suggesting that SAA is involved in early lesion development. The decreased atherosclerosis in the Saa-/-Ldlr-/- mice occurred despite increased levels of blood monocytes and was independent of plasma lipid levels. SAA is produced predominantly by hepatocytes and macrophages. To determine which source of SAA may have a dominant role in lesion development, bone marrow transplantation was performed. Ldlr-/- mice that received bone marrow from Saa-/-Ldlr-/- mice had slightly reduced ascending aorta atherosclerosis compared with Saa-/-Ldlr-/- mice receiving bone marrow from Ldlr-/- mice, indicating that the expression of SAA by macrophages may have an important influence on atherogenesis.
CONCLUSIONS: The results indicate that SAA produced by macrophages promotes early lesion formation in the ascending aorta.
Document Type
Article
Publication Date
7-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.1161/JAHA.115.001858
Funding Information
This work was supported by NIH grant P01 HL092969, the Leducq Foundation and the Cardiovascular Pathophysiology and Biochemistry Training grant HL007237.
Repository Citation
Krishack, Paulette A.; Bhanvadia, Clarissa V.; Lukens, John; Sontag, Timothy J.; de Beer, Maria C.; Getz, Godfrey S.; and Reardon, Catherine A., "Serum Amyloid A Facilitates Early Lesion Development in Ldlr-/- Mice" (2015). Physiology Faculty Publications. 67.
https://uknowledge.uky.edu/physiology_facpub/67
Notes/Citation Information
Published in Journal of the American Heart Association, v. 4, no. 7, article e001858, p. 1-15.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.