Research Topics
Genomes and Genes
| DANIEL JAMES RADERSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
Molecular regulation of HDL metabolism and function: implications for novel therapiesDaniel J Rader
Institute for Translational Medicine and Therapeutics, Cardiovascular Institute, and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
J Clin Invest 116:3090-100. 2006..Advances in our understanding of the molecular regulation of HDL metabolism, macrophage cholesterol efflux, and HDL function will lead to a variety of novel therapeutics...- Approach to the patient with extremely low HDL-cholesterolDaniel J Rader
Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 11 125 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
J Clin Endocrinol Metab 97:3399-407. 2012..Uncommon encounters with patients exhibiting extremely low HDL-C provide an opportunity to directly observe the role of HDL metabolism in atherosclerosis and beyond the vascular system... 
Secreted miRNAs suppress atherogenesisDaniel J Rader
Cardiovascular Institute and the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Perelman School of Medicine, 11 125 Translational Research Center, Philadelphia, Philadelphia 19104 5156, USA
Nat Cell Biol 14:233-5. 2012....- IL-1 and atherosclerosis: a murine twist to an evolving human storyDaniel J Rader
Department of Medicine and Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania 19104 5158, USA
J Clin Invest 122:27-30. 2012..These findings illustrate the complexity of inflammatory pathways in atherosclerosis and suggest the need for careful calibration of antiinflammatory approaches to atherosclerosis... - Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acidsJaime L Lecker
Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
Lipids Health Dis 10:186. 2011..1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w])... 
Gene transfer of wild-type apoA-I and apoA-I Milano reduce atherosclerosis to a similar extentCorinna Lebherz
Department of Pathology and Laboratory Medicine, Gene Therapy Program, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Cardiovasc Diabetol 6:15. 2007..We therefore sought to compare the two forms of apoA-I using liver-directed somatic gene transfer in hypercholesterinemic mice--a model which is most adequately mimicking the clinical setting...
Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2Uwe J F Tietge
Univ of Pennsylvania Medical Center, 654 BRB II III, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
Am J Physiol Endocrinol Metab 285:E403-11. 2003..These data suggest a novel metabolic role for sPLA2: modification of HDL during the APR to promote increased adrenal uptake of HDL cholesteryl ester to serve as source for steroid hormone synthesis...- Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatinDaniel J Rader
University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Am J Cardiol 91:20C-23C; discussion 23C-24C. 2003..001). Mean percent reductions from baseline in the LDL cholesterol/HDL cholesterol ratio were 52%, 39%, and 30% for rosuvastatin 10 mg, simvastatin 20 mg, and pravastatin 20 mg, respectively, in these 2 trials... - Effects of nonstatin lipid drug therapy on high-density lipoprotein metabolismDaniel J Rader
Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Am J Cardiol 91:18E-23E. 2003..The mechanisms by which nonstatin pharmacologic agents increase HDL cholesterol are not completely understood but probably involve multiple mechanisms for each class... - Inhibition of cholesteryl ester transfer protein activity: a new therapeutic approach to raising high-density lipoproteinDaniel J Rader
Center for Experimental Therapeutics and Department of Medicine, University of Pennsylvania School of Medicine, 654 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Curr Atheroscler Rep 6:398-405. 2004.... - Translating molecular discoveries into new therapies for atherosclerosisDaniel J Rader
Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRBII III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Nature 451:904-13. 2008.... - Liver X receptor and farnesoid X receptor as therapeutic targetsDaniel J Rader
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
Am J Cardiol 100:n15-9. 2007..FXR modulators or antagonists could potentially lower LDL cholesterol levels and even modulate high-density lipoprotein metabolism. FXR is a complicated but fascinating target for the development of new therapeutic approaches... - Regulation of reverse cholesterol transport and clinical implicationsDaniel J Rader
Preventive Cardiology Lipid Research Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA
Am J Cardiol 92:42J-49J. 2003..This article focuses on new developments in the regulation of reverse cholesterol transport and the clinical implications of those developments... - Mechanisms of disease: HDL metabolism as a target for novel therapiesDaniel J Rader
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Nat Clin Pract Cardiovasc Med 4:102-9. 2007..The goal of new approaches is to either raise HDL-cholesterol levels or improve the function of HDL. Here, the current status of the development of novel therapies targeted toward HDL metabolism is reviewed... - Lipases as modulators of atherosclerosis in murine modelsRobert J Brown
Department of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Curr Drug Targets 8:1307-19. 2007..The following chapter reviews the physiology of these lipases, and the consequences of the loss or gain of function for each lipase in modulating atherosclerosis, with emphasis on murine models... - Novel approaches to the treatment of dyslipidemiaDaniel J Rader
University of Pennsylvania Medical Center, 654 BRBII/III, Philadelphia, PA 19104-6160, USA
Arterioscler Thromb Vasc Biol 25:480-1. 2005 - Endothelial lipase: a new member of the triglyceride lipase gene familyD J Rader
University of Pennsylvania School of Medicine, Department of Medicine, Philadelphia, USA
Curr Opin Lipidol 11:141-7. 2000.... - The endothelium and lipoproteins: insights from recent cell biology and animal studiesD J Rader
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
Semin Thromb Hemost 26:521-8. 2000..Although a great deal is known about endothelial-lipoprotein interactions, more research is needed in this important area... - Gene therapy for familial hypercholesterolemiaD J Rader
Departments of Medicine, Pathology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Nutr Metab Cardiovasc Dis 11:40-4. 2001..Once these vectors are available, effective clinical gene therapy for homozygous FH is likely to become a clinical reality... - Genes influencing HDL metabolism: new perspectives and implications for atherosclerosis preventionD J Rader
University of Pennsylvania Medical Center, 614 BRBII III 421 Curie Blvd, Philadelphia, PA 19104, USA
Mol Med Today 6:170-5. 2000..Here, we will discuss those components of the high density lipoprotein metabolism and lipid transport pathways that are potential preventative or therapeutic targets for ASCVD... - Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell?Daniel J Rader
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Cell Metab 1:223-30. 2005..We suggest that atherogenic lipoproteins promote and anti-atherogenic lipoproteins inhibit atherogenesis by modulating macrophage function in a variety of ways beyond cholesteryl ester accumulation and foam cell formation... - Genetic basis of atherosclerosis: insights from mice and humansIoannis M Stylianou
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRBII III Labs, 421 Curie Boulevard, Philadelphia, Pennsylvania, 19104 6160, USA
Circ Res 110:337-55. 2012..The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches... - High-density lipoproteins and atherosclerosisDaniel J Rader
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Cardiol 90:62i-70i. 2002..Yet, the mechanisms by which HDL inhibits atherosclerosis are not yet fully understood. There remains much to be learned about HDL metabolism and its relation to atherosclerosis and other cardiovascular risk factors... - Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitusDaniel J Rader
Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Med 120:S12-8. 2007..Primary care physicians play a critical role in the early identification and treatment of patients at increased risk for the development of type 2 diabetes and CVD because of their obesity and associated complications... - Therapy to reduce risk of coronary heart diseaseDaniel J Rader
Preventive Cardiology and Lipid Clinic, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Clin Cardiol 26:2-8. 2003..Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum... - The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosisDaniel J Rader
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, and Children s Hospital of Philadelphia, Philadelphia, PA, USA
J Lipid Res 50:S189-94. 2009.... - Endothelial lipase promotes the catabolism of ApoB-containing lipoproteinsUli C Broedl
University of Pennsylvania, Philadelphia, PA, USA
Circ Res 94:1554-61. 2004..In light of these results, inhibition of EL has the potential to raise levels of atherogenic lipoproteins in addition to HDL-C levels... - Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammationRyan E Moore
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Circ Res 97:763-71. 2005.... - A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesityPrakash Seshadri
Department of Internal Medicine, Division of Endocrinology, University of Pennsylvania Health System, Philadelphia 19104, USA
Am J Med 117:398-405. 2004..Both diets had similar effects on LDL and HDL subfractions... - Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalphaMichael Lehrke
Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Cell Metab 1:297-308. 2005.... - Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivoSnehal U Naik
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Circulation 113:90-7. 2006..In the present study we used this approach to test the hypothesis that administration of the synthetic LXR agonist GW3965 would increase the rate of macrophage RCT in vivo... - In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol effluxPatricia G Yancey
Division of Gastroenterology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
J Lipid Res 45:337-46. 2004..These findings indicate that the type of lipase acting on HDL in vivo will determine which FC efflux pathway the HDL serves. Additionally, the extent of lipolysis will determine the efficiency of FC removal via this pathway... - Determining hepatic triglyceride production in mice: comparison of poloxamer 407 with Triton WR-1339John S Millar
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
J Lipid Res 46:2023-8. 2005..Another nonionic detergent, poloxamer 407 (P-407), also inhibits LPL. In these studies, we demonstrate that P-407 is comparable to Triton in the determination of TG production but without the unwanted side effects of Triton... - Coronary artery calcification at electron beam computed tomography is increased in asymptomatic type 2 diabetics independent of traditional risk factorsMegan L Wolfe
Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, 815 BRB2/3, Philadelphia, PA 19104, USA
J Cardiovasc Risk 9:369-76. 2002.... - Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemiaLei Zhao
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 277:35350-6. 2002..The data provide support for a novel mechanism linking the 12/15-lipoxygenase pathway to a known immunomodulatory Th1 cytokine in atherogenesis... - Fish oil promotes macrophage reverse cholesterol transport in miceTomoyuki Nishimoto
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Arterioscler Thromb Vasc Biol 29:1502-8. 2009..The aim of this study was to investigate the effects of FO on the process of macrophage reverse cholesterol transport (RCT) in an in vivo mouse model... - The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower in African Americans than in CaucasiansMarina Cuchel
Department of Medicine, University of Pennsylvania, School of Medicine, 654 BRB II III, 421 Curie Blvd, Philadelphia, PA 19104, USA
Atherosclerosis 163:169-74. 2002.... - Impact of combined deficiency of hepatic lipase and endothelial lipase on the metabolism of both high-density lipoproteins and apolipoprotein B-containing lipoproteinsRobert J Brown
Department of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA
Circ Res 107:357-64. 2010..Hepatic lipase (HL) and endothelial lipase (EL) are extracellular lipases that both hydrolyze triglycerides and phospholipids and display potentially overlapping or complementary roles in lipoprotein metabolism... - Effects of nonlipolytic ligand function of endothelial lipase on high density lipoprotein metabolism in vivoUli C Broedl
University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA
J Biol Chem 278:40688-93. 2003..Our study demonstrates for the first time that EL has both a lipolytic and nonlipolytic function in HDL metabolism in vivo. Lipolytic activity of EL, however, seems to be most important for its effects on systemic HDL metabolism... - Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipaseCyrille Maugeais
Departments of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Circulation 108:2121-6. 2003..Overexpression of endothelial lipase (EL) markedly reduces plasma levels of HDL cholesterol and apoA-I in mice, but the mechanisms of this effect remain unknown... - Knockdown of acyl-CoA:diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in miceYing Liu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
Biochim Biophys Acta 1781:97-104. 2008..Our findings indicate that the majority of TG destined for secretion by liver is synthesized by DGAT2 and suggests that DGAT2 may be a therapeutic target for treatment of hypertriglyceridemia, hepatic steatosis and obesity... - Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivoYuzhen Zhang
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Circulation 108:661-3. 2003.... - The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humansBonnie Ky
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
J Am Coll Cardiol 51:1653-62. 2008..The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma... - Managing diabetic dyslipidemia: beyond statin therapyHemanth Neeli
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Curr Diab Rep 9:11-7. 2009.... - Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transportHiroyuki Tanigawa
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA
Circulation 116:1267-73. 2007.... - Modulation of HDL metabolism by the niacin receptor GPR109A in mouse hepatocytesXiaoyu Li
Institute for Translational Medicine and Therapeutics and Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Biochem Pharmacol 80:1450-7. 2010..These results indicate that niacin-mediated activation of GP109A in liver lowers ABCA1 expression leading to reduced hepatic cholesterol efflux to HDL... - Angiopoietin-like protein 3 inhibits lipoprotein lipase activity through enhancing its cleavage by proprotein convertasesJun Liu
Translational Medicine and Therapeutics and Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 285:27561-70. 2010..These novel findings provide a new paradigm of specific protease-substrate interaction and further improve our knowledge of LPL biology... - Structural and functional consequences of the Milano mutation (R173C) in human apolipoprotein A-IEric T Alexander
Gastroenterology Nutrition Hepatology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 4318, USA
J Lipid Res 50:1409-19. 2009.... - CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient miceLiang Zhao
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Arterioscler Thromb Vasc Biol 28:1283-9. 2008..The purpose of this study was to distinguish the contributions of CD44 expressed on bone marrow-derived and non-bone marrow-derived cells to atherosclerosis... - Discovery and validation of new molecular targets in treating dyslipidemia: the role of human geneticsAmit V Khera
Institute for Translational Medicine and Therapeutics and Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Trends Cardiovasc Med 19:195-201. 2009..This application of genetic epidemiology, termed Mendelian randomization, may prove useful in informing ongoing drug development efforts... - Role of N-linked glycosylation in the secretion and activity of endothelial lipaseGwen C Miller
Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Lipid Res 45:2080-7. 2004..The Asn-373 mutant demonstrated a 3-fold decrease in bridging compared with wild-type EL, whereas Asn-116 and Asn-471 were similar to wild-type EL... - Human secretory phospholipase A2 mediates decreased plasma levels of HDL cholesterol and apoA-I in response to inflammation in human apoA-I transgenic miceUwe J F Tietge
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Arterioscler Thromb Vasc Biol 22:1213-8. 2002..Secretory phospholipase A2 (sPLA2), an acute-phase protein, may play a key role in the pathophysiology of this phenomenon... - Combined effects of cholesterol reduction and apolipoprotein A-I expression on atherosclerosis in LDL receptor deficient miceMasa-aki Kawashiri
Department of Medicine, University of Pennsylvania Medical Center, School of Medicine, 654 Biomedical Research Building II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA
Atherosclerosis 165:15-22. 2002.... - The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysmLei Zhao
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA
Nat Med 10:966-73. 2004..These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route... - COX-2-derived prostacyclin confers atheroprotection on female miceKarine M Egan
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA
Science 306:1954-7. 2004..This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females... - Lecithin: cholesterol acyltransferase expression has minimal effects on macrophage reverse cholesterol transport in vivoHiroyuki Tanigawa
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Circulation 120:160-9. 2009.... - Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activationDevashish Kothapalli
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 6084, USA
J Clin Invest 113:609-18. 2004..Our results identify the Cox-2 gene as a target of APOE signaling, link HDL and APOE to IP action, and describe a potential new basis for the cardioprotective effect of HDL and APOE... - Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemiaFrederick F Samaha
Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Nat Clin Pract Cardiovasc Med 5:497-505. 2008..We tested the safety and LDL-cholesterol-lowering efficacy of an MTP inhibitor, AEGR-733 (Aegerion Pharmaceuticals Inc., Bridgewater, NJ), alone and in combination with ezetimibe... - Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trialLeAnne T Bloedon
Division of General Internal Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA
J Am Coll Nutr 27:65-74. 2008..We studied the effects of flaxseed on markers of cardiovascular risk in hypercholesterolemic adults... - Both the peroxisome proliferator-activated receptor delta agonist, GW0742, and ezetimibe promote reverse cholesterol transport in mice by reducing intestinal reabsorption of HDL-derived cholesterolFrançois Briand
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Clin Transl Sci 2:127-33. 2009..In conclusion, PPARdelta activation enhances excretion of macrophage or HDL-derived cholesterol in feces through reduced NPC1L1 expression in mice, comparable to the effect of ezetimibe... - Apolipoprotein E suppresses the type I inflammatory response in vivoKamilah Ali
Institute for Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
Circ Res 97:922-7. 2005..This implies that apoE selectively regulates TLR4- and TLR3-mediated signaling of IL-12 production. These results indicate that apoE modulates the T helper-1-type immune response in vivo by modulating IL-12 production... - Update on the role of endothelial lipase in high-density lipoprotein metabolism, reverse cholesterol transport, and atherosclerosisTomoyuki Yasuda
Institute for Translational Medicine and Therapeutics and Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Circ J 74:2263-70. 2010..The available data regarding the impact of EL expression and activity on HDL metabolism, reverse cholesterol transport, and atherosclerosis are reviewed... - Endothelial lipase is less effective at influencing HDL metabolism in vivo in mice expressing apoA-IIUli C Broedl
Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
J Lipid Res 47:2191-7. 2006..We conclude that the presence of apoA-II on HDL particles inhibits the ability of EL to influence the metabolism of HDL in vivo... - Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humansAndrew C Edmondson
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
J Clin Invest 119:1042-50. 2009..Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C... - Persistent liver expression of murine apoA-l using vectors based on adeno-associated viral vectors serotypes 5 and 1Ken Kitajima
Institute for Translational Medicine and Therapeutics, University of Pennsylvania Medical Center, 654 BRBII III Labs, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
Atherosclerosis 186:65-73. 2006..Furthermore, AAV1-based vectors generate higher apoA-l levels than AAV5-based vectors. It is possible that the levels of expression achieved using these vectors will be therapeutic in preventing atherosclerosis... - Intensive versus moderate lipid lowering with statins after acute coronary syndromesChristopher P Cannon
Thrombolysis in Myocardial Infarction TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
N Engl J Med 350:1495-504. 2004..Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear... - CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout miceGuipeng An
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Room 1254 BRBII III, 421 Curie Blvd, Philadelphia, PA 19104, USA
Mol Immunol 46:1702-9. 2009..The protective role of CD59 was gender-biased and most likely involved prevention of MAC-mediated vascular injury, with possible contribution from an undefined effect on plasma cholesterol homeostasis... - On-statin cholesteryl ester transfer protein mass and risk of recurrent coronary events (from the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 [PROVE IT-TIMI 22] study)Amit V Khera
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
Am J Cardiol 106:451-6. 2010..This finding is consistent with CETP facilitating reverse cholesterol transport in the setting of robust LDL clearance and might have important implications for efforts to optimally target patients with pharmacologic CETP inhibition... - Effects of rosiglitazone on lipids, adipokines, and inflammatory markers in nondiabetic patients with low high-density lipoprotein cholesterol and metabolic syndromeFrederick F Samaha
Cardiovascular Division, Department of Medicine, Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, PA, USA
Arterioscler Thromb Vasc Biol 26:624-30. 2006..However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-gamma agonists have not been fully tested in nondiabetic patients with metabolic syndrome... - Apolipoprotein A-I deficiency results in markedly increased atherosclerosis in mice lacking the LDL receptorRyan E Moore
University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA
Arterioscler Thromb Vasc Biol 23:1914-20. 2003..CONCLUSIONS: These results demonstrate that despite normal levels of HDL-C, apoA-I deficiency is associated with a significant loss of protection from the formation of atherosclerosis in LDLR-/- mice fed a chow diet... - Lipases and HDL metabolismWeijun Jin
University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA
Trends Endocrinol Metab 13:174-8. 2002..Here, we focus on new developments and insights into the role of secreted lipases on HDL metabolism and their relationship to atherosclerosis... - Microsomal prostaglandin E synthase-1 deletion suppresses oxidative stress and angiotensin II-induced abdominal aortic aneurysm formationMiao Wang
Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
Circulation 117:1302-9. 2008..Deletion of mPGES-1 modulates experimentally evoked pain and inflammation and retards atherogenesis. The role of mPGES-1 in abdominal aortic aneurysm is unknown... - Glycosylation of endothelial lipase at asparagine-116 reduces activity and the hydrolysis of native lipoproteins in vitro and in vivoRobert J Brown
Department of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Lipid Res 48:1132-9. 2007..These data suggest that N-linked glycosylation at Asn-116 reduces the ability of EL to hydrolyze lipids in LDL and HDL2... - Emerging therapies targeting high-density lipoprotein metabolism and reverse cholesterol transportDanielle Duffy
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Circulation 113:1140-50. 2006 - Complete prevention of atherosclerosis in apoE-deficient mice by hepatic human apoE gene transfer with adeno-associated virus serotypes 7 and 8Ken Kitajima
Institution for Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Arterioscler Thromb Vasc Biol 26:1852-7. 2006.... - The roles of different pathways in the release of cholesterol from macrophagesMaria Pia Adorni
Gastroenterology, Hepatology, and Nutrition Division, Children s Hospital of Philadelphia, Philadelphia, PA, USA
J Lipid Res 48:2453-62. 2007..Another pathway that is present in all cells is aqueous diffusion. Our studies demonstrate that this mechanism is one of the major contributors to efflux, particularly in cholesterol-normal cells... - CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humansMichael Lehrke
Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Am Coll Cardiol 49:442-9. 2007..This study was designed to determine the association of CXCL16 with inflammation, atherosclerosis, and acute coronary syndromes... - An inflammatory cascade leading to hyperresistinemia in humansMichael Lehrke
Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
PLoS Med 1:e45. 2004..CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states... - Pharmacologic suppression of hepatic ATP-binding cassette transporter 1 activity in mice reduces high-density lipoprotein cholesterol levels but promotes reverse cholesterol transportShigenori Yamamoto
Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
Circulation 124:1382-90. 2011..The aim of the present study was to test the hypothesis that probucol inhibits hepatic ABCA1 activity, thereby reducing HDL-C levels but promoting RCT from macrophages... - Peroxisome proliferator-activated receptor-α activation promotes macrophage reverse cholesterol transport through a liver X receptor-dependent pathwayKazuhiro Nakaya
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Arterioscler Thromb Vasc Biol 31:1276-82. 2011..However, it remains unclear whether PPARα activation promotes macrophage RCT in vivo... - Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiencyKatsunori Ikewaki
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Lipid Res 45:1302-11. 2004.... - Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]William J Cain
Department of Biological Sciences, University of Delaware, Newark, DE, USA
J Lipid Res 46:2681-91. 2005..Our studies indicate that apo[a] is the primary ligand that mediates Lp[a] uptake and plasma clearance... - Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammationAmin Majdalawieh
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Sir Charles Tupper Medical Building, Halifax, NS, Canada B3H 1X5
Proc Natl Acad Sci U S A 103:2346-51. 2006..Thereby, we speculate that AEBP1 may be critically implicated in the development of atherosclerosis, and it may serve as a molecular target toward developing antiinflammatory, antiatherogenic therapeutic approaches... - Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipaseOuliana Ziouzenkova
Cardiovascular Division, Brigham and Women s Hospital, Harvard University, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:2730-5. 2003.... - Expression of human hepatic lipase in the rabbit model preferentially enhances the clearance of triglyceride-enriched versus native high-density lipoprotein apolipoprotein A-IShirya Rashid
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada
Circulation 107:3066-72. 2003.... - The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysmAnna Helgadottir
deCODE Genetics, Sturlugata 8, IS 101 Reykjavik, Iceland
Nat Genet 40:217-24. 2008..These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases... - 'Multipurpose oxidase' in atherogenesisDaniel J Rader
Nat Med 13:1146-7. 2007 - Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterolMargaret E Brousseau
Lipid Research Laboratory, Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111, USA
N Engl J Med 350:1505-15. 2004..Inhibition of cholesteryl ester transfer protein (CETP) has been proposed as a strategy to raise HDL cholesterol levels... - New insights into the regulation of HDL metabolism and reverse cholesterol transportGary F Lewis
Department of Medicine and Physiology, University of Toronto, Canada
Circ Res 96:1221-32. 2005.... - A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemiaA David Marais
Groote Schuur Hospital and University of Cape Town, Lipidology, Internal Medicine, 5th Floor C Barnard Building, UCT Health Science Faculty, Anzio Road, Cape Town 7925, South Africa
Atherosclerosis 197:400-6. 2008..All treatments were well tolerated. Rosuvastatin may have therapeutic value in the management of hoFH... - Genetics of increased HDL cholesterol levels: insights into the relationship between HDL metabolism and atherosclerosisMarina Cuchel
Arterioscler Thromb Vasc Biol 23:1710-2. 2003 - Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosisPhilip J Barter
Hanson Institute and the Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia
Arterioscler Thromb Vasc Biol 23:160-7. 2003..Thus, it seems important and timely to test the hypothesis in randomized trials of humans that pharmacological inhibition of CETP retards the development of atherosclerosis... - Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretionMargaret E Brousseau
Lipid Metabolism Laboratory, JM USDA HNRCA at Tufts University and Tufts New England Medical Center, Boston, Mass 02111, USA
Arterioscler Thromb Vasc Biol 25:1057-64. 2005..The present study was designed to address these issues... - Rosuvastatin improves the atherogenic and atheroprotective lipid profiles in patients with hypertriglyceridemiaDonald B Hunninghake
Heart Disease Prevention Clinic, University of Minnesota, Minneapolis, Minnesota 55455, USA
Coron Artery Dis 15:115-23. 2004..We examined the effects of rosuvastatin treatment on triglyceride levels and lipid measures in a parallel-group multicenter trial (4522IL/0035) in patients with hypertriglyceridemia (Fredrickson Type IIb or IV)... - Evidence that hepatic lipase and endothelial lipase have different substrate specificities for high-density lipoprotein phospholipidsMyNgan Duong
Department of Medicine, University of Adelaide, North Terrace, Australia
Biochemistry 42:13778-85. 2003..These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids... - A variant in CDKAL1 influences insulin response and risk of type 2 diabetesValgerdur Steinthorsdottir
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Nat Genet 39:770-5. 2007..The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion... - Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissueDagmar Kratky
Institute of Molecular Biosciences, University of Graz, Graz, Austria
J Clin Invest 115:161-7. 2005..Our results suggest that EL activity in AT and other peripheral tissues might contribute to the tissue uptake of free fatty acids, which could have important implications for the metabolism of plasma lipoproteins... - N-Glycosylation regulates endothelial lipase-mediated phospholipid hydrolysis in apoE- and apoA-I-containing high density lipoproteinsDanielle Skropeta
Lipid Research Group, Heart Research Institute, Camperdown, New South Wales 2050, Australia
J Lipid Res 48:2047-57. 2007..These data show that individual N-linked glycans have unique and important effects on the phospholipase activity and substrate specificity of EL... - NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterolSuzanne Benjannet
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 279:48865-75. 2004..In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion...
Research Grants
- Gordon Research Conference: Lipoprotein Metabolism 2004Daniel Rader; Fiscal Year: 2004....
- MECHANISM OF PI-RELATED DYSLIPIDEMIA AND ATHEROSCLEROSISDaniel Rader; Fiscal Year: 2004..These studies will provide novel insights into the mechanisms of PI-associated dyslipidemia and atherosclerosis. ..
- Mentored Career Development in Patient Oriented ResearchDaniel Rader; Fiscal Year: 2006..abstract_text> ..
- High Density Lipoprotein Metabolism Influence of Extracellular PhospholipasesDaniel Rader; Fiscal Year: 2007..The results of these studies should provide important new insight into the role of EL in HDL metabolism and atherogenesis. ..
- Genetics of Elevated High Density Lipoprotein CholesterolDaniel Rader; Fiscal Year: 2009..We hypothesize that our GWA approach will serve to identify novel genes that cause or predispose to high HDL, generating new targets for HDL raising therapies. ..
- HDL metabolism: Influence of extracellular lipasesDaniel Rader; Fiscal Year: 2009....
- Genetics of Elevated High Density Lipoprotein CholesterolDANIEL JAMES RADER; Fiscal Year: 2010..We hypothesize that our GWA approach will serve to identify novel genes that cause or predispose to high HDL, generating new targets for HDL raising therapies. ..
- HDL metabolism: Influence of extracellular lipasesDaniel Rader; Fiscal Year: 2009....
- Genetics of lipoprotein metabolism and CVD in CKDDANIEL JAMES RADER; Fiscal Year: 2010..The outcome is likely to provide novel approaches to predicting CVD risk in CKD and potentially new targets for therapeutic intervention. ..
- CELLULAR BASIS OF ANTIATHEROGENESIS BY APOLIPOPROTEIN EDaniel Rader; Fiscal Year: 2001..These studies will provide greater understanding of the role of the local inflammatory response in atherosclerosis and its regulation by apoE. ..
- HDL METABOLISM:INFLUENCE OF EXTRACELLULAR PHOSPHOLIPASESDaniel Rader; Fiscal Year: 2003....
- Effects of Niacin on Lp(a), Oxidized LDL, and inflammation in the AIM-HIGH trialDANIEL JAMES RADER; Fiscal Year: 2010..We also seek to find out more information about how the adverse effects of niacin occur and how genetic diversity may play a role in individual responses to niacin. (End of Abstract) ..