Haizhao Yan1, Manabu Niimi1, Chuan Wang1,2, Yajie Chen1,3, Huanjin Zhou1, Fumikazu Matsuhisa4, Kazutoshi Nishijima5, Shuji Kitajima4, Bo Zhang6, Hiroshi Yokomichi7, Katsuyuki Nakajima8, Masami Murakami8, Jifeng Zhang9, Y Eugene Chen9, Jianglin Fan1,3. 1. Department of Molecular Pathology, Faculty of Medicine, Graduate School of Interdisciplinary Research, University of Yamanashi. 2. Department of Pharmacology, College of Pharmacy, Shaanxi University of Chinese Medicine. 3. School of Biotechnology and Health Sciences, Wuyi University. 4. Analytical Research Center for Experimental Sciences, Saga University. 5. Animal Research Laboratory, Bioscience Education-Research Support Center, Akita University. 6. Department of Biochemistry, Fukuoka University School of Medicine. 7. Department of Health Sciences, University of Yamanashi. 8. Department of Clinical Laboratory Medicine, Graduate School of Medicine, Gunma University. 9. Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center.
Abstract
AIM: Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect. METHODS: To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tg rabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis. RESULTS: With Tg and non-Tg rabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tg rabbits. Moreover, Tg rabbits exhibited faster clearance of DiI-labeled β-VLDLs than non-Tg rabbits. CONCLUSION: The results of our study suggest that the enhancement of β-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tg rabbits.
AIM: Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect. METHODS: To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tgrabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis. RESULTS: With Tg and non-Tgrabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tgrabbits. Moreover, Tgrabbits exhibited faster clearance of DiI-labeled β-VLDLs than non-Tgrabbits. CONCLUSION: The results of our study suggest that the enhancement of β-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tgrabbits.
Authors: Kenneth C-W Yu; Christopher David; Sujata Kadambi; Andreas Stahl; Ken-Ichi Hirata; Tatsuro Ishida; Thomas Quertermous; Allen D Cooper; Sungshin Y Choi Journal: J Lipid Res Date: 2004-06-01 Impact factor: 5.922
Authors: Benjamin F Voight; Gina M Peloso; Marju Orho-Melander; Ruth Frikke-Schmidt; Maja Barbalic; Majken K Jensen; George Hindy; Hilma Hólm; Eric L Ding; Toby Johnson; Heribert Schunkert; Nilesh J Samani; Robert Clarke; Jemma C Hopewell; John F Thompson; Mingyao Li; Gudmar Thorleifsson; Christopher Newton-Cheh; Kiran Musunuru; James P Pirruccello; Danish Saleheen; Li Chen; Alexandre F R Stewart; Arne Schillert; Unnur Thorsteinsdottir; Gudmundur Thorgeirsson; Sonia Anand; James C Engert; Thomas Morgan; John Spertus; Monika Stoll; Klaus Berger; Nicola Martinelli; Domenico Girelli; Pascal P McKeown; Christopher C Patterson; Stephen E Epstein; Joseph Devaney; Mary-Susan Burnett; Vincent Mooser; Samuli Ripatti; Ida Surakka; Markku S Nieminen; Juha Sinisalo; Marja-Liisa Lokki; Markus Perola; Aki Havulinna; Ulf de Faire; Bruna Gigante; Erik Ingelsson; Tanja Zeller; Philipp Wild; Paul I W de Bakker; Olaf H Klungel; Anke-Hilse Maitland-van der Zee; Bas J M Peters; Anthonius de Boer; Diederick E Grobbee; Pieter W Kamphuisen; Vera H M Deneer; Clara C Elbers; N Charlotte Onland-Moret; Marten H Hofker; Cisca Wijmenga; W M Monique Verschuren; Jolanda M A Boer; Yvonne T van der Schouw; Asif Rasheed; Philippe Frossard; Serkalem Demissie; Cristen Willer; Ron Do; Jose M Ordovas; Gonçalo R Abecasis; Michael Boehnke; Karen L Mohlke; Mark J Daly; Candace Guiducci; Noël P Burtt; Aarti Surti; Elena Gonzalez; Shaun Purcell; Stacey Gabriel; Jaume Marrugat; John Peden; Jeanette Erdmann; Patrick Diemert; Christina Willenborg; Inke R König; Marcus Fischer; Christian Hengstenberg; Andreas Ziegler; Ian Buysschaert; Diether Lambrechts; Frans Van de Werf; Keith A Fox; Nour Eddine El Mokhtari; Diana Rubin; Jürgen Schrezenmeir; Stefan Schreiber; Arne Schäfer; John Danesh; Stefan Blankenberg; Robert Roberts; Ruth McPherson; Hugh Watkins; Alistair S Hall; Kim Overvad; Eric Rimm; Eric Boerwinkle; Anne Tybjaerg-Hansen; L Adrienne Cupples; Muredach P Reilly; Olle Melander; Pier M Mannucci; Diego Ardissino; David Siscovick; Roberto Elosua; Kari Stefansson; Christopher J O'Donnell; Veikko Salomaa; Daniel J Rader; Leena Peltonen; Stephen M Schwartz; David Altshuler; Sekar Kathiresan Journal: Lancet Date: 2012-05-17 Impact factor: 79.321