Andrew Levy, MD, PhD
Professor of Cardiovascular Biology
MD PhD, 1990 - John Hopkins University, USA
Understanding the apparent failure of therapies aimed at raising vitamin E and high density lipoprotein in individuals with Diabetes Mellitus
80% of individuals with Diabetes Mellitus die due to cardiovascular disease. Accordingly, over $200 billion is spent annually on treating vascular complications of diabetes in the USA alone. This public health and economic burden demands development of inexpensive and effective therapeutic tools. Our laboratory is focused on understanding the scientific basis for the apparent failure of therapies aimed at raising vitamin E and high density lipoprotein (HDL) as demonstrated in over 30 clinical trials. We have identified that such therapeutic approaches demonstrate considerable benefit when targeted to diabetic individuals with a copy number variant in the haptoglobin gene.
An important innovative concept that is being intensively investigated in the lab is the mechanism whereby HDL can be transformed into a proatherogenic (promotes plaque formation) and dysfunctional entity by the tethering of extra corpuscular hemoglobin to the HDL. Furthermore, we are examining how this transformation can be prevented or reversed.
Veiner HL, Gorbatov R, Vardi M, Doros G, Miller-Lotan R, Zohar Y , Sabo E, Asleh R, Levy NS, Goldfarb LJ , Berk T, Haas T, Shalom H , Suss-Toby E , Kam A, Kaplan M , Tamir R, Ziskind A and Levy AP. 2015. Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability. Atherosclerosis 239, 232-239.
Asleh R, Ward J, Levy NS, Safuri S, Aronson D, and Levy AP. 2014. Haptoglobin genotype dependent differences in macrophage lysosomal oxidative injury. J Biol Chem 289, 16313-16325.
Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, Anbinder Y, Lache O, Nakhoul FM, Asaf R, Farbstein D, Pollak M, Solveitchik YZ, Strauss M, Alshiek J, Livshits A. Schwartz A, Awad H, Jad K, and Goldstein H. 2010. Haptoglobin: basic and clinical aspects. Antioxidant redox signaling. 12, 293-304.
Orchard TJ, Sun W, Cleary P, Lachin JM, McGee P, Patterson AD, Raskin P, Anbinder Y, and Levy AP. 2013. Haptoglobin genotype and the rate of function decline in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Diabetes 62, 3218-3223.
Vardi M, Levy NS, and Levy AP. 2013. Vitamin E in the prevention of cardiovascular disease-the importance of proper patient selection. J Lipid Research 54, 2307-2314.
Measurement of atherosclerotic plaque volume in transgenic Haptoglobin 2-2 mice in vivo using micro-ultrasound.
AA (aortic arch), BC (brachiocephalic artery), CC (common carotid), SC (subclavian), DA (Descending aorta). Arrow points to an atherosclerotic plaque at the brachiocephalic aortic arch junction that can be followed over time in the same mouse by high resolution microultrasound. This mouse model enables assessment of therapies designed to reduce atherosclerotic plaque growth and prevent plaque rupture.