LIPID RESEARCH GROUOP - Research
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Our group's research focuses on the mechanism responsible for LDL oxidation as related to macrophage foam cell formation and atherosclerosis development. Unique contribution of our group to this field is the elucidation of the roles of pro-oxidants and of anti-oxidants which are associated with LDL and with arterial cells, in macrophage-mediated oxidation of LDL and in atherogenesis. Anti-oxidants studies include lipoprotein- and cell-associated flavonoids (from pomegranate, red wine, olive oil and licorice), vitamin E and carotenoids (such as ,ß-carotene and tomatoe’s lycopene), as well as the macrophage glutathione system. The role of paraoxonases (PONs) in protection against oxidative stress and atherosclerosis is also studied in Aviram’s laboratory. Methodologies in use in the lab include cell culture, animal models for atherosclerosis (apo E and PON knockout mice), and human nutritional and pharmacological intervention studies.
12,700 Citations of ~ 400 articles
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1. Aviram M., S. Lund-Katz, M. Phillips, and A. Chait. J. Biol. Chem. 263: 16842-16848 (1988).
2. Aviram M., E.L., Bierman, and A. Chait. J. Biol. Chem. 263:15416-15422 (1988).
3. Aviram M., S. Keidar, M. Rosenblat and J.G. Brook. J. Biol Chem. 266: 11567-11574 (1991).
4. Aviram M. J. Biol. Chem. 267:218-225 (1992).
5. Aviram M. and I. Maor. J. Clin. Invest. 91:1942-1952 (1993).
6. Maor I., H. Mandel and M. Aviram. Arterioscler Thromb Vasc Biol. 15: 1378-1387 (1995).
7. Maor I., Hayek T., Coleman R. and Aviram M. Arterioscler. Thromb. Vasc. Biol. 7:2995-3005 (1997).
8. Kaplan M., Williams K., Mandel H. and Aviram M. Arterioscler. Thromb. Vasc. Biol. 18:542-553 (1998).
9. Kaplan M and Aviram M. Arterioscler. Thromb. Vasc. Biol. 21 : 386 – 393 (2001).
10. Aviram M. and Vaya J. Methods in Enzymology 335: 244-256 (2001).
11. Rosenblat M. and Aviram M. Atherosclerosis 160: 69 – 80 (2002).
12. Rosenblat M., Coleman R. and Aviram M. Atherosclerosis 163: 17-28 (2002).
13. Aviram M and Rosenblat M. In: Redox Genome Interactions in Health and Disease. Fuchs J, Podda M and Packer L (Eds). Marcel Dekker, NY (Pub.) pp. 557 – 590 (2004).
14. Hayek T., Hussein K., Aviram M., Coleman R., Kediar S., Pavlotzky E., and Kaplan M. Atherosclerosis 183: 25-33 (2005).
15. Coleman R., Hayek T., Keidar S. and Aviram M. Acta Histochemica. 108: 415-424 (2006).
16. Hayek T., Kaplan M., Karry R. and Aviram M. Atherosclerosis 195: 277-286 (2007).
17. Fuhrman B., Partoush A., Volkova N. and Aviram M. Atherosclerosis 196: 598-607 (2008).
18. Fuhrman B., Gantman A., Khateeb J., Volkova N., Horke S., Kivan J., Dumler I., and Aviram M. Cardiovasc. Res. 84: 145-154 (2009).
19. Rosenblat M, Volkova N, Roqueta-Rivera M, Nakamura MT, Aviram M. Atherosclerosis 2010 (in press).
Oxidative stress is thought to play a key role in the development of atherosclerosis, the major cause of morbidity and mortality in the world. We have shown in atherosclerotic mice and in humans that LDL oxidation, as well as additional lipoprotein modifications contribute to enhanced atherogenicity of LDL. Studies on the mechanisms of oxidized LDL (Ox-LDL) retention to extracellular matrix (ECM) proteoglycans as related to the lipoprotein uptake by the macrophage scavenger receptors, leading to cellular accumulation of cholesterol and oxysterols, are carried out in our laboratory. Macrophage – mediated oxidation of LDL and foam cell formation are the hallmark of early atherogenesis, and we have demonstrated the role of cellular oxygenases and oxidases (NADPH oxidase), as well as that of macrophage antioxidants (such as the glutathione system), in LDL oxidation. We have demonstrated that under oxidative stress, not only the lipoproteins are oxidized, but also the cellular lipids. We showed the presence of Ox-LDL and that of lipid peroxidized macrophages in the atherosclerotic lesion, and demonstrated that these oxidized cells are able to oxidize LDL even in the absence of transition metal ions. Finally, we have shown increased LDL oxidation in patients with increased risk for atherosclerosis development (hypercholesterolemia, hypertension, diabetes, chronic renal failure). Drug therapy in these patients (hypocholesterolemic “statins”, ACE inhibitors, Insulin) reduced the patient’s increased LDL oxidation and atherogenic characteristics.
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1. Fuhrman B., A. Lavy and M. Aviram. Am. J. Clin. Nutr. 61: 549-554 (1995).
2. Fuhrman B., Buch S., Vaya J., Belinky P.A., Coleman R., Hayek T. and Aviram M. Am. J. Clin. Nutr. 66:267-275 (1997).
3. Rosenblat M., Belinky P., Vaya J., Levy R., Hayek T., Coleman R., Merchav S. and Aviram M. J. Biol. Chem. 274: 13790-13799 (1999).
4. Aviram M., Dornfeld L., Rosenblat M., Volkova N., Kaplan M., Hayek T., Presser D. and Fuhrman B. Am. J. Clin. Nutr. 71: 1062-1076 (2000).
5. Fuhrman B. and Aviram M. Curr. Opin. Lipidol. 12: 41-48 (2001).
6. Aviram M., Rosenbalt M., Gaitini D., Nitecki S., Hoffman A., Dornfeld L., Volkova N., Presser D., Attias J., Leiker H. and Hayek T. Clinical Nutrition 23:423-433 (2004).
7. Fuhrman B., Volkova N. and Aviram M. J Nutr Biochem 16:570-576 (2005).
8. Rosenblat M, Volkova N, Coleman M, Aviram M. J Agric Food Chem. 54: 1928-1935 (2006).
9. Rozenberg O., Howell A. and Aviram M. Atherosclerosis. 188: 68-76 (2006).
10. Rosenblat M., Volkova N. Coleman R and Aviram M. Atherosclerosis 195: e61-68 (2007).
11. Aviram M., Volkova N., Coleman R., Reddy M.K., Ferreira D. and Rosenblat M. J Agric Food Chem. 56: 1148-1157 (2008).
12. Davidson MH., Maki KC., Dicklin MR.,Feinstein SB., Witchger MS., Bell M., DeLemos J., Provost JC., Liker H, and Aviram M. Am j Cardiol. 104: 936-942 (2009).
13. Fuhrman B, Volkova N, Aviram M. Nutrition 26(4):359-366 (2010)

Dietary antioxidants that inhibit LDL oxidation can attenuate atherosclerosis development , and we have demonstrated indeed such properties for vitamin E, carotenoids (lycopene, ß-carotene), but mainly for polyphenolic flavonoids, such as those found in pomegranate (punicalagin, an hydrolyzable tannins), wine (querchetine flavonol and resveratrol), licorice (glabridin isoflavan) , and olive oil (oleoropein phenolic). We have provided evidence that the inhibitory effect of some flavonoids on LDL oxidation (and on atherosclerosis development) is related to their interaction with the lipoprotein directly, as well as to their accumulation in arterial macrophages and subsequent inhibition of cellular oxygenases and oxidases.

Video: Pomegranate Juice Antioxidative Effect (Hebrew)
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1. Aviram M., Rosenblat M., Bisgaier C.L., Newton R.S., Primo-Parmo S.L., and La Du B.N.: J. Clin. Invest. 101:1581-1590 (1998).
2. Aviram M. Mol. Med. Today. 5 (9):381-386 (1999).
3. Aviram M., Hardak E., Vaya J., Mahmood S., Milo S., Hoffman A., Billecke S.S, Dragonov D. and Rosenblat M. Circulation 101:2510-2517 (2000).
4. Fuhrman B., Volkova N. and Aviram M. Atherosclerosis. 161:307-316 (2002).
5. Rozenberg O., Rosenblat M., Coleman R., Shih D.M. and Aviram M. Free Radic Biol Med 34:774-784 (2003).
6. Rozenberg O., Shih D.M. and Aviram M. Arterioscl Thromb Vasc Biol 23:461-467 (2003).
7. Rosenblat M., Draganov D., Watson C.E., Bisgaier C.L., La Du B.N. and Aviram M. Arterioscl Thromb Vasc Biol 23: 468-474 (2003).
8. Rosenblat M., Hayek T., Hussein K and Aviram M. Arterioscl Thromb Vasc Biol 24:175-180 (2004).
9. Aviram M and Rosenblat M. Free Radic. Biol. Med. 37:1304–1316 (2004).
10. Rosenblat M., Shih D., Vaya J. and Aviram M. Atherosclerosis 179:69-77 (2005).
11. Rozenberg O., Shih D. and Aviram M. Atherosclerosis 181:9-18 (2005).
12. Shamir R, Hartman C, Karry R , Pavlotzki E, Eliakim R, Lachter J, Swissa A, and Aviram M. Free Radic Biol Med 39:336-344 (2005).
13. Rosenblat M, Gaidukov L, Khersonsky O, Vaya J, Oren R, Tawfik DS, Aviram M. J. Biol. Chem. 281: 7657-7665 (2006).
14. Rosenblat M., Karry R. and Aviram M. Atherosclerosis.187:74-81 (2006).
15. Shiner M., Fuhrman B. and Aviram M. Biochem. Biophys. Res. Commun. 349: 1094–1099 (2006).
16. Rozenberg O., Aviram M. Biochem. Biophys. Res. Commun. 18:492-498 (2006).
17. Fuhrman B., Khateeb J., Shiner M., Nitzan O., Karry R., Volkova N. and Aviram M. Arterioscl. Thromb. Vasc. Biol. 28:1361-1367 (2008).
18. Rosenblat M, Coleman R, Reddy ST, Aviram M. J Lipid Res. 50:870-879 (2009).
19. Fuhrman B, Gantman A, Aviram M. Atherosclerosis 2010 (in press).
Under excess oxidative stress, antioxidants capability to block the formation of Ox-LDL and cellular oxidized lipids formation may not be sufficient. We have recently demonstrated that HDL - associated Paraoxonase (PON1) can hydrolyze oxidized lipids in oxidized lipoproteins, macrophages, and in atherosclerotic lesion, and thus may act as a second line of defense against oxidative stress. Combination of potent antioxidants (some unique flavonoids) together with paraoxonase was shown in our laboratory to attenuate atherogenesis, secondary to reduced oxidative stress and to decreased macrophage uptake of oxidized lipoproteins via the scavenger receptors.
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