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Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice.
Circulation. 2004 Aug 03; 110(5):540-5.Circ

Abstract

BACKGROUND

Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels.

METHODS AND RESULTS

Female LDL-receptor-null (LDLR-/-) mice were fed high-saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (P<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (P<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (r=0.49; P<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (r=0.66; P<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (r=0.65; P<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein.

CONCLUSIONS

Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans.

Authors+Show Affiliations

Department of Medicine, University of Washington, Seattle, Wash 98195-6426, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15277327

Citation

Lewis, Katherine E., et al. "Increase in Serum Amyloid a Evoked By Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice." Circulation, vol. 110, no. 5, 2004, pp. 540-5.
Lewis KE, Kirk EA, McDonald TO, et al. Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice. Circulation. 2004;110(5):540-5.
Lewis, K. E., Kirk, E. A., McDonald, T. O., Wang, S., Wight, T. N., O'Brien, K. D., & Chait, A. (2004). Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice. Circulation, 110(5), 540-5.
Lewis KE, et al. Increase in Serum Amyloid a Evoked By Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice. Circulation. 2004 Aug 3;110(5):540-5. PubMed PMID: 15277327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice. AU - Lewis,Katherine E, AU - Kirk,Elizabeth A, AU - McDonald,Thomas O, AU - Wang,Shari, AU - Wight,Thomas N, AU - O'Brien,Kevin D, AU - Chait,Alan, Y1 - 2004/07/26/ PY - 2004/7/28/pubmed PY - 2005/2/5/medline PY - 2004/7/28/entrez SP - 540 EP - 5 JF - Circulation JO - Circulation VL - 110 IS - 5 N2 - BACKGROUND: Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels. METHODS AND RESULTS: Female LDL-receptor-null (LDLR-/-) mice were fed high-saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (P<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (P<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (r=0.49; P<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (r=0.66; P<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (r=0.65; P<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein. CONCLUSIONS: Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15277327/Increase_in_serum_amyloid_a_evoked_by_dietary_cholesterol_is_associated_with_increased_atherosclerosis_in_mice_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000136819.93989.E1?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -