University of Miami,
Keywords: atherosclerotic heart disease
Summary:Atherosclerotic heart disease, the single deadliest disease in the United States, develops as a result of plaque buildup in the intima of vasculature due to excess cholesterol-rich lipoproteins, dysfunctions associated with lipid removal, inflammatory responses, transition of smooth muscle cells (SMCs) from contractile to synthetic phenotype due to mitochondrial dysfunctions, oxidative stress, and pro-inflammatory signals resulting in encapsulation of foam cells beneath a fibrous cap (1). Two major events that promote the so-called "plaque vulnerability" are plaque destabilization and rupture. High-density lipoprotein (HDL) popularly termed as “good cholesterol,” along with apolipoproteins such as apoA-I, participate in extracellular cholesterol efflux. However, efficient removal of lipids also depends on the intracellular lipid transport. Macrophages take up excess cholesterol, and the delivery of cholesterol to the mitochondria of liver cells is one of the rate-determining steps for cholesterol degradation in the liver. Furthermore, treatment modalities which can result in therapeutic outcome should have the ability to control plaque rupture, inflammatory responses, and prevent SMC phenotypic transition, and overall plaque regression. Treatment of such a condition can be carried out either by inhibiting lipid biosynthesis or by enhancing lipid clearance from the body. The ability to detect vulnerable plaques has the benefit to enhance treatment regimes. Magnetic resonance imaging (MRI) plays important role in cardiovascular imaging (2). We are developing self-therapeutic and diagnostic combo nano-assemblies (3) that enable MR imaging of atherosclerotic plaques in addition to lipid removal from the body by following intra and extra lipid transport pathways. Acknowledgements: This work was supported, in whole or in part, by the National Institutes of Health Grant R56HL121392 from National Heart, Lung, and Blood Institute and American Heart Association National Scientist Award 14SDG18690009, and Sylvester Comprehensive Cancer Center to S.D. References: 1. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801-809. 2. Fleg JL, et al. (2012) Detection of High-Risk Atherosclerotic Plaque: Report of the NHLBI Working Group on Current Status and Future Directions. JACC. Cardiovascular imaging 5(9):941-955. 3. Marrache S & Dhar S (2013) Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis. Proceedings of the National Academy of Sciences 110(23):9445-9450.