Michael Aviram, DSc
Professor of Biochemistry
MSc, 1975 - Technion-Israel Institute of Technology, Haifa
DSc, 1978 - Technion-Israel Institute of Technology, Haifa
HDL – associated Paraoxonases (PONs) and cardiovascular diseases
Oxidative stress is considered to play a key role in the development of atherosclerosis,which leads to cardiovascular diseases, the major cause of morbidity and mortality in the world. Oxidative stress leads to the oxidation of blood and arterial components such as low density lipoprotein (LDL), high density lipoprotein (HDL) and monocyte – derived macrophages. Dietary and endogenous antioxidants that inhibit such oxidation have the potential to attenuate atherosclerosis development.We have shown that antioxidant rich nutrients such as pomegranate (POM) or red wine polyphenols, serve as a first line of defense against oxidative stress. Furthermore, our studies have revealed that a second line of defense is provided by the paraoxonase 1 (PON1) enzyme in the serum. PON1 is an HDL-associated esterase/lactonase that protects against oxidative stress, not by inhibiting lipid peroxidation, but by breaking down specific derivatives of oxidized lipids. At the cellular level, PON2 behaves similarly to circulatory serum PON1. Most recently we have focused on understanding the regulation of PONs at both the humoral (serum) and cellular (arterial macrophages) levels. In particular we want to investigate how dietary antioxidants, as well as anti atherosclerotic drugs (including hypolipidemic, anti diabetic, and hypotensive drugs) influence PONs activities. A better appreciation of PON regulation could point to new targets for treating cardiovascular diseases.
(Upper panel) The development of macrophages into atherosclerotic foam cells is influenced by cholesterol, oxidative stress, glucose, triglycerides, or hypertension. This development is inhibited by statins, antioxidants, insulin, fibrates, or hypotensive drugs respectively, as well as by Paraoxonases (PONs).
(Lower panel) The Mediteranean Pyramid is enriched with polyphenolic dietary antioxidants and provides protection against cardiovascular diseases.
Rosenblat M, Volkova N, Paland N, and Aviram M. 2013. Triglyceride accumulation in macrophages upregulates paraoxonase 2 (PON2) expression via ROS-mediated JNK/c-Jun signaling pathway activation. BioFactors. 38,458-469
Rosenblat M, Volkova N, Aviram M. 2013. Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. 226, 110-7
Aviram M and Rosenblat M. 2012. Pomegranate Protection against Cardiovascular Diseases. Evid Based Complement Alternat Med (eCAM). 12:382763, doi: 10.1155/2012/382763.