Journal of Vascular Medicine & Surgery

Prevention and interference of atherosclerotic heart disease - New insights and directions

World Congress on Vascular Diseases, Medicine & Surgeons Summit

October 24-25, 2016 Chicago, USA

Subroto Chatterjee

Johns Hopkins University, USA

Posters & Accepted Abstracts: Vasc Med Surg

Abstract:

We have previously observed that the levels of blood cholesterol and sugar containing lipids called glycosphingolipids (GSL) rise and fall in tandem upon plasma exchange therapy in patients homozygous for familial hypercholesterolemia (FH). Moreover, cultured skin fibroblasts from LDL receptor negative FH subjects were unable to metabolize GSL/Lactosylceramide-associated with LDL efficiently compared to normal fibroblasts having functional LDL receptors. Such findings rationalized our approach to inhibit GSL synthesis as a novel approach to mitigate atherosclerotic heart disease. In a series of experiments, recently described in the journal Circulation, we have identified and halted the action of GSL and cholesterol. Using an inhibitor of GSL synthesis we could block abnormal cholesterol production, transport, breakdown and improve bile acid production successfully thus preventing and interfering atherosclerotic heart disease in a poE-/- mice and normal rabbits fed a western diet, rich in cholesterol and triglycerides. In particular, the blood levels of oxidized LDL, LDL cholesterol and triglycerides were decreased and the level of HDL cholesterol was increased. Treatment markedly decreased arterial calcification and vascular wall stiffness. Recently, we have remarkably improved on the efficacy of the GSL inhibitor to prevent and interfere with atherosclerotic heart disease by way of encapsulating it within a biodegradable polymer which allows rapid absorption in the gut and slow release of drug over a period of days instead of hours. Thus inhibition of GSL synthesis is useful to ameliorate atherosclerotic heart disease and GSL synthesis inhibition an alternative to the use of family of statins and PCSK-9 antibody.

Biography :

Email: schatte2@jhmi.edu