Research Topics
| Jonathan SmithSummaryAffiliation: Cleveland Clinic Foundation Country: USA Publications
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Detail Information
Publications
Physiological difference in autophagic flux in macrophages from 2 mouse strains regulates cholesterol ester metabolismPeggy Robinet
Cleveland Clinic, Lerner Research Institute NC10, 9500 Euclid Ave, Cleveland, OH 44195
Arterioscler Thromb Vasc Biol 33:903-10. 2013..When autophagy was activated by amino acid starvation, CE levels decreased in DBA/2 cells. CONCLUSIONS: Physiological regulation of autophagy in macrophages controls CE accumulation and may modify atherosclerosis susceptibility...- Low prevalence of connexin-40 gene variants in atrial tissues and blood from atrial fibrillation subjectsGregory D Tchou
Department of Cell Biology, 9500 Euclid Ave, Cleveland, OH 44106, USA
BMC Med Genet 13:102. 2012..The prevalence of nonsynonymous Cx40 mutations in blood and atrial tissue was also compared to mutation frequencies reported in prior studies... - High-density lipoprotein function, dysfunction, and reverse cholesterol transportEdward A Fisher
Department of Cardiovascular Medicine, New York University School of Medicine, New York, NY 444195, USA
Arterioscler Thromb Vasc Biol 32:2813-20. 2012..Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels... - Red blood cells play a role in reverse cholesterol transportKimberly T Hung
Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA
Arterioscler Thromb Vasc Biol 32:1460-5. 2012..Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT... 
Transcriptome profile of macrophages from atherosclerosis-sensitive and atherosclerosis-resistant miceJonathan D Smith
Department of Cell Biology, Cleveland Clinic Foundation, Ohio, 44195, USA
Mamm Genome 17:220-9. 2006..The combination of this expression profiling data with the genetic method of quantitative trait locus mapping should give powerful insights into the genes that affect atherosclerosis susceptibility in mice...- Potential use of estrogen-like drugs for the prevention of Alzheimer's diseaseJonathan D Smith
Department of Cell Biology, NC10, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Mol Neurosci 20:277-81. 2003..It is not known whether this combination of hormones or the late age at which the therapy was administered was responsible for the adverse outcome... - Dysfunctional HDL as a diagnostic and therapeutic targetJonathan D Smith
Department of Cell Biology, Cleveland Clinic, Cleveland, OH 44195, USA
Arterioscler Thromb Vasc Biol 30:151-5. 2010..These studies provide the basis for the development of an oxidant-resistant form of apoAI and clinical measures of HDL modification and dysfunction, which may be useful as a treatment criterion... - Atherosclerosis susceptibility loci identified from a strain intercross of apolipoprotein E-deficient mice via a high-density genome scanJonathan D Smith
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
Arterioscler Thromb Vasc Biol 26:597-603. 2006..This study aimed to determine the genetic regions associated with strain effects on lesion area... - Apolipoprotein A-I and its mimetics for the treatment of atherosclerosisJonathan D Smith
Cleveland Clinic, Department of Cell Biology, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Curr Opin Investig Drugs 11:989-96. 2010.... - Myeloperoxidase, inflammation, and dysfunctional high-density lipoproteinJonathan D Smith
Department of Cell Biology, Box NC10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Clin Lipidol 4:382-8. 2010.... - Identification of atherosclerosis-modifying genes: pathogenic insights and therapeutic potentialJonathan D Smith
Cleveland Clinic Lerner College of Medicine, Department of Cell Biology, Cleveland Clinic, Cleveland, OH 44195, USA
Expert Rev Cardiovasc Ther 4:703-9. 2006..This review will summarize the methods and results thus far in the identification of atherosclerosis-modifier genes... - Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular diseaseLemin Zheng
Department of Cell Biology, Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Clin Invest 114:529-41. 2004..They also suggest a potential mechanism for MPO-dependent generation of a proatherogenic dysfunctional form of HDL in vivo... - Lack of mitogen-activated protein kinase phosphatase-1 protects ApoE-null mice against atherosclerosisJianzhong Shen
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA
Circ Res 106:902-10. 2010..Multiple protein kinases have been implicated in cardiovascular disease; however, little is known about the role of their counterparts: the protein phosphatases... - Localization of nitration and chlorination sites on apolipoprotein A-I catalyzed by myeloperoxidase in human atheroma and associated oxidative impairment in ABCA1-dependent cholesterol efflux from macrophagesLemin Zheng
Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195, USA
J Biol Chem 280:38-47. 2005.... - ApoE promotes the proteolytic degradation of AbetaQingguang Jiang
Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Neuron 58:681-93. 2008..GW3965 treatment also reversed contextual memory deficits. These data demonstrate a mechanism through which ApoE facilitates the clearance of Abeta from the brain and suggest that LXR agonists may represent a novel therapy for AD... - Sex specific gene regulation and expression QTLs in mouse macrophages from a strain intercrossJeffrey M Bhasin
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio, United States of America
PLoS ONE 3:e1435. 2008..A powerful way to identify genes for complex traits it to combine genetic and genomic methods. Many trait quantitative trait loci (QTLs) for complex traits are sex specific, but the reason for this is not well understood... - Apolipoprotein A-I tryptophan substitution leads to resistance to myeloperoxidase-mediated loss of functionDao Quan Peng
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA
Arterioscler Thromb Vasc Biol 28:2063-70. 2008..We tried to determine which residues mediated this inactivation and create an oxidant-resistant apoAI variant... - Moderately decreased cholesterol absorption rates are associated with a large atheroprotective effectMichael E Greenberg
Institute of Genomic Medicine, Cleveland Clinic, Ohio 44195, USA
Arterioscler Thromb Vasc Biol 29:1745-50. 2009..We examined the efficacy of a moderate decrease in cholesterol absorption in preventing atherosclerosis formation in the mouse... - Tyrosine modification is not required for myeloperoxidase-induced loss of apolipoprotein A-I functional activitiesDao Quan Peng
Department of Cell Biology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 280:33775-84. 2005..Thus, tyrosine modification of apoAI is not required for its MPO-mediated inhibition of cholesterol acceptor activity... - Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particleArundhati Undurti
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA
J Biol Chem 284:30825-35. 2009.... - Supervised principal component analysis for gene set enrichment of microarray data with continuous or survival outcomesXi Chen
Department of Quantitative Health Sciences, The Cleveland Clinic, 9500 Euclid Ave Cleveland, OH 44195, USA
Bioinformatics 24:2474-81. 2008..SOFTWARE: The R code for the analysis used in this article are available upon request, we are currently working on implementing the proposed method in an R package... - ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-IJonathan D Smith
Department of Cell Biology NC10, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Lipid Res 45:635-44. 2004..Finally, we could not reproduce a two-step effect on lipid efflux using conditioned medium from ABCA1-expressing cells pretreated with cyclodextrin... - Drug discovery: estrogen-related compounds in mouse models of Alzheimer's diseaseJonathan D Smith
Department of Cell Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Mol Neurosci 24:145-7. 2004..In this position paper, we review these data, along with our own--using estrogens in a transgenic mouse model of AD--and introduce our current working hypothesis and research... - In silico quantitative trait locus map for atherosclerosis susceptibility in apolipoprotein E-deficient miceJonathan D Smith
Rockefeller University, New York, NY, USA
Arterioscler Thromb Vasc Biol 23:117-22. 2003.... - Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian populationGong Qing Shen
Department of Molecular Cardiology, Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
J Hum Genet 53:144-50. 2008..These results indicate that chromosome 9p21 confers risk for development of MI in an Italian population... - Quantitative trait locus mapping for atherosclerosis susceptibilityJonathan Smith
Department of Cell Biology, The Clevelanf Clinic Foundation, Cleveland, Ohio 44195, USA
Curr Opin Lipidol 14:499-504. 2003..This review describes an unbiased genetic mapping method called quantitative trait locus mapping and progress in using this method to identify genes that alter atherosclerosis susceptibility in mice... - Genetic susceptibility to myocardial infarction and coronary artery diseaseEric J Topol
Department of Genetics, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, BRB 724, 10900 Euclid Avenue, Cleveland, OH 44106 4955, USA
Hum Mol Genet 15:R117-23. 2006..Although the population attributable risk for any of the genes identified to date is limited, such discovery is likely to be accelerated in the future... - Drug library screen to identify compounds that decrease secreted Abeta from a human cell lineEnakshi Chakrabarti
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
Curr Alzheimer Res 2:255-9. 2005.... - Direct electrochemical evaluation of plasma membrane cholesterol in live mammalian cellsDechen Jiang
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
J Am Chem Soc 129:11352-3. 2007 - The refined structure of nascent HDL reveals a key functional domain for particle maturation and dysfunctionZhiping Wu
Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, NE 10, Cleveland, Ohio 44195, USA
Nat Struct Mol Biol 14:861-8. 2007.... 
Synthesis and biological evaluation of analogues of a novel inhibitor of beta-amyloid secretionEnakshi Chakrabarti
Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
J Med Chem 53:5302-19. 2010..The analogue with the best permeability was evaluated in 2-month old amyloid precursor protein transgenic mice and found to acutely reduce cerebral Abeta levels by 40% after a single iv administration...- Large disk intermediate precedes formation of apolipoprotein A-I-dimyristoylphosphatidylcholine small disksKeng Zhu
Department of Cell Biology, Cleveland Clinic, Ohio 44195, USA
Biochemistry 46:6299-307. 2007..Thus, the formation of small apoA-I lipid disks proceeds through the formation of a large disk intermediate... - Apolipoprotein A-I lysine modification: effects on helical content, lipid binding and cholesterol acceptor activityGregory Brubaker
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Biochim Biophys Acta 1761:64-72. 2006.... - Identification of the cAMP-responsive enhancer of the murine ABCA1 gene: requirement for CREB1 and STAT3/4 elementsWilfried Le Goff
Dept of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Arterioscler Thromb Vasc Biol 26:527-33. 2006..To determine the mechanism by which expression of the murine ABCA1 gene is highly induced by cAMP analogues... - Cyclosporin A traps ABCA1 at the plasma membrane and inhibits ABCA1-mediated lipid efflux to apolipoprotein A-IWilfried Le Goff
Department of Cell Biology NC10, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Arterioscler Thromb Vasc Biol 24:2155-61. 2004..CONCLUSIONS: ABCA1 inhibition by cyclosporin A supports a role for ABCA1 endocytic trafficking in ABCA1-mediated lipid efflux and could explain in part the low HDL levels observed in some patients with transplants... - Quantitative assay for mouse atherosclerosis in the aortic rootJulie Baglione
Department of Cell Biology, The Cleveland Clinic Foundation, OH, USA
Methods Mol Med 129:83-95. 2006..Here, we provide the detailed methods for the quantitative analysis of mouse aortic root lesion area... - A novel folding intermediate state for apolipoprotein A-I: role of the amino and carboxy terminiEitan Gross
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Biophys J 90:1362-70. 2006..Our findings suggest that the N-terminus of apoAI stabilizes the native state of the protein by increasing the Eyring energy barrier for the N --> I(equil) unfolding transition; whereas the carboxyl terminus destabilizes that state... - Thrombospondin-4 regulates vascular inflammation and atherogenesisElla G Frolova
Department of Molecular Cardiology and Joseph J Jacob Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Ohio 44195, USA
Circ Res 107:1313-25. 2010..Thrombospondin (TSP)-4 is an extracellular protein that has been linked to several cardiovascular pathologies. However, a role for TSP-4 in vascular wall biology remains unknown... - Reevaluation of the role of the multidrug-resistant P-glycoprotein in cellular cholesterol homeostasisWilfried Le Goff
Department of Cell Biology NC10, Cleveland Clinic Foundation, Cleveland, OH, USA
J Lipid Res 47:51-8. 2006.... - Human cerebrospinal fluid apolipoprotein E isoforms are apparently inefficient at complexing with synthetic Alzheimer's amyloid-[beta] peptide (A[beta] 1-40 ) in vitroZhongmin Zhou
Laboratory of Alzheimer Research, Department of Neurology and Neuroscience, Cornell University Medical College, New York, USA
Mol Med 8:376-81. 2002.... - 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic miceJustine A Levin-Allerhand
The Rockefeller University, New York, NY, USA
J Alzheimers Dis 4:449-57. 2002..The increased efficacy of 17alpha-estradiol versus 17beta-estradiol may help to develop safe and effective therapeutics... - Confirmation of the microsomal triglyceride transfer protein genetic effect on lipids in young African American men from the CARDIA studySuh-Hang Hank Juo
Arterioscler Thromb Vasc Biol 23:912-3. 2003 - Ovariectomy of young mutant amyloid precursor protein transgenic mice leads to increased mortalityJustine A Levin-Allerhand
The Rockefeller University, New York, NY 10021, USA
J Mol Neurosci 19:163-6. 2002..Previous studies have demonstrated increased mortality in mice overexpressing mutant or wildtype APP independent of A beta accumulation; thus, estrogen withdrawal may potentiate this phenotype associated with APP overexpression... - Evaluation of the role of phosphatidylserine translocase activity in ABCA1-mediated lipid effluxJonathan D Smith
Rockefeller University, New York, New York 10021, USA
J Biol Chem 277:17797-803. 2002..Although ABCA1 induction was associated with a small increase in cell surface PS, these results argue against the notion that this cell surface PS is sufficient to mediate cellular apoAI binding and lipid efflux... - Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomicsPing Zheng
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA
Biochim Biophys Acta 1676:41-50. 2004..These studies demonstrate that comparative sequence analysis is a successful strategy to predict candidate regulatory regions in vivo, although they do not imply that this element controls apoE expression physiologically... - Aging, gender and APOE isotype modulate metabolism of Alzheimer's Abeta peptides and F-isoprostanes in the absence of detectable amyloid depositsJun Yao
Department of Psychiatry, New York University, The Nathan S Kline Institute for Psychiatric Research, Orangeburg, New York, USA
J Neurochem 90:1011-8. 2004.... - A phenotype-sensitizing Apoe-deficient genetic background reveals novel atherosclerosis predisposition loci in the mouseHayes M Dansky
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10021, USA
Genetics 160:1599-608. 2002..In summary, two independently performed crosses between C57BL/6 and FVB/N Apoe-deficient mice have revealed several previously unreported atherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels... - Decreased atherosclerosis in mice deficient in tumor necrosis factor-alpha receptor-II (p75)Unni M Chandrasekharan
Arterioscler Thromb Vasc Biol 27:e16-7. 2007 - The murine macrophage apoB-48 receptor gene (Apob-48r): homology to the human receptorMatthew L Brown
Department of Medicine, Division of Gerontology and Geriatrics, University of Alabama at Birmingham, Birmingham, AL 35294 0012, USA
J Lipid Res 43:1181-91. 2002.... - Apolipoproteins and aging: emerging mechanismsJonathan D Smith
Lab Biochem Gen and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Ageing Res Rev 1:345-65. 2002..One variant of apoE (E4) is associated with increased risk for heart disease, stroke and Alzheimer's disease (AD). In addition, some of the potential mechanisms for the observed effects of apoE on aging will be discussed... - Expression of the carrier protein apolipoprotein D in the mouse inner earMichael S Hildebrand
Department of Gene Identification and Expression, Murdoch Childrens Research Institute, Royal Children s Hospital, Flemington Road, Parkville, Melbourne, VIC 3052, Australia
Hear Res 200:102-14. 2005..The mouse was found to have a hearing threshold that was not significantly different to the control strain... - Safe and effective method for chronic 17beta-estradiol administration to miceJustine A Levin-Allerhand
Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Contemp Top Lab Anim Sci 42:33-5. 2003.... - Dietary methionine effects on plasma homocysteine and HDL metabolism in miceWanda Velez-Carrasco
Department of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021, USA
J Nutr Biochem 19:362-70. 2008..Mice on methionine diets had >20% decreased body weights and decreased HDL-C levels. An HDL turnover study demonstrated that the HDL-C production rate was significantly reduced in mice fed the methionine diet... - Insight into ABCG1-mediated cholesterol effluxJonathan D Smith
Arterioscler Thromb Vasc Biol 26:1198-200. 2006 - Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in miceZhenglong Wang
Program for Vascular Biology and Therapeutics and Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520 8066, USA
J Clin Invest 118:195-204. 2008..These results demonstrate what we believe to be a novel role for PLC activity in promoting macrophage survival in atherosclerotic plaques and identify PLC beta3 as a potential target for treatment of atherosclerosis...
Research Grants
- Macrophage lipid efflux and atherosclerosisJonathan Smith; Fiscal Year: 2004..These studies will add to our knowledge about the mechanism of reverse cholesterol transport and its antiatherogenic role, and may lead to novel therapeutic strategies to prevent atherosclerosis in humans ..
- ABCA1, ApoAI, and Lipid EffluxJonathan Smith; Fiscal Year: 2007..In addition, this study will include the identification of the apoAl oxidative modification by the enzyme myeloperoxidase that diminishes its lipid acceptor activity. ..
- Characterization of Atherosclerosis Modifier GenesJonathan D Smith; Fiscal Year: 2010..These may lead to diagnostic tools, novel drug targets, and therapies to prevent or treat CAD. Thus, the proposed studies address a significant health concern and offer hope for new modes of risk assessment and prevention. ..