Henry N. Ginsberg
New York, USA
The EAS is delighted to announce that one of the two Keynote Lectures at the 2017 EAS Congress in Prague will be given by Henry N. Ginsberg, MD, the Irving Professor of Medicine and Director Emeritus of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center.
Professor Ginsberg’s research interests have centered on regulation of the metabolism of apolipoprotein B–containing lipoproteins in cells, mice, and humans. His present work focuses on the interaction between the secretion of very low-density lipoproteins by the liver and hepatic steatosis, as well as human mutations affecting hepatic lipid and lipoprotein metabolism. He recently received an Outstanding Investigator Award from NIH.
Professor Ginsberg has been a key contributor to the success of EAS as Co-Chair, with Professor John Chapman (Pitié-Salpetriere University Hospital, Paris, France), of the EAS Consensus Panel. Since its inception in 2009, the EAS Consensus Panel has addressed topical questions in key areas of cardiovascular disease research. The EAS Consensus Panel has helped to raise awareness of familial hypercholesterolaemia, establish lipoprotein(a) as a cardiovascular risk factor, as well as focus on the appropriate management of statin-associated muscle symptoms (SAMS). Full details are available at: http://www.eas-society.org/?page=sams_consensus
Tue 25 Apr
Mechanistic insights into innovative therapeutics in lipid lowering in vivo
In his Keynote Lecture, Professor Ginsberg will discuss mechanistic insights into innovative therapeutics in lipid lowering in vivo. Dyslipidaemia, a major risk factor for cardiovascular disease, is characterized by elevated levels of atherogenic apolipoprotein B100 (apoB) lipoproteins. Novel therapeutic approaches that inhibit either proprotein convertase subtilisin/kexin type (PCSK9) or cholesteryl ester transfer protein (CETP) have been shown to substantially reduce plasma levels of low-density lipoprotein cholesterol (LDL-C) and apoB. While preclinical and in vitro studies are informative, the effects of these treatments on lipoprotein metabolism in vivo have until recently been poorly defined.
Recent research has addressed this issue. Studies have shown that PCSK9 inhibitors achieve their lipid effects by concomitant increases in the fractional catabolic rates of intermediate-density lipoprotein- and LDL-apoB, and reduction in the synthesis of LDL-apoB, consistent with preclinical findings. Decreases in plasma levels of LDL-C and apoB associated with CETP inhibition with anacetrapib was explained solely by an increase in the fractional clearance rate of LDL-apoB, without any effect on LDL-apoB synthesis. Such studies have been critical in definitively establishing the mechanism(s) of these novel therapies on lipoprotein metabolism in vivo. If ongoing clinical trials show that these treatments translate to reduction in cardiovascular outcomes, then these mechanisms are likely to contribute to this.
Reyes-Soffer G, Pavlyha M, Ngai C, Thomas T, Holleran S, Ramakrishnan R, Karmally W, Nandakumar R, Fontanez N, Obunike JC, Marcovina SM, Lichtenstein AH, Matthan NR, Matta J, Maroccia M, Becue F, Poitiers F, Swanson B, Cowan L, Sasiela WJ, Surks HK, Ginsberg HN. Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans. Circulation 2016 Dec 16. pii: CIRCULATIONAHA.116.025253. [Epub ahead of print]
Reyes-Soffer G, Millar JS, Ngai C, Jumes P, Coromilas E, Asztalos B, Johnson-Levonas AO, Wagner JA, Donovan DS, Karmally W, Ramakrishnan R, Holleran S, Thomas T, Dunbar RL, deGoma EM, Rafeek H, Baer AL, Liu Y, Lassman ME, Gutstein DE, Rader DJ, Ginsberg HN. Cholesteryl Ester Transfer Protein inhibition with anacetrapib decreases fractional clearance rates of high-density lipoprotein apolipoprotein A-I and plasma cholesteryl ester transfer protein. Arterioscler Thromb Vasc Biol 2016;36:994-1002.
Reyes-Soffer G, Moon B, Hernandez-Ono A, Dionizovik-Dimanovski M, Jimenez J, Obunike J, Thomas T, Ngai C, Fontanez N, Donovan DS, Karmally W, Holleran S, Ramakrishnan R, Mittleman RS, Ginsberg HN. Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans. Sci Transl Med 2016;8:323ra12.