Research Topics
Genomes and Genes | Marlys L KoschinskySummaryAffiliation: Queen's University Country: Canada Publications
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Publications
Identification of sequences in apolipoprotein(a) that maintain its closed conformation: a novel role for apo(a) isoform size in determining the efficiency of covalent Lp(a) formationLev Becker
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6
Biochemistry 43:9978-88. 2004....- Novel insights into Lp(a) physiology and pathogenicity: more questions than answers?Marlys L Koschinsky
Department of Biochemistry, A208 Botterell Hall, Queen s University, Kingston, Ontario Canada K7L 3N6
Cardiovasc Hematol Disord Drug Targets 6:267-78. 2006..Future directions in the field as well as recommendations for the use of Lp(a) in clinical contexts will also be addressed... - Analysis of the mechanism of lipoprotein(a) assemblyM L Koschinsky
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
Clin Genet 52:338-46. 1997.... - Lipoprotein(a) and the link between atherosclerosis and thrombosisMarlys L Koschinsky
Department of Biochemistry, Queen s University, Kingston, Ontario
Can J Cardiol 20:37B-43B. 2004..As such, Lp(a) constitutes a functional link not only between atherosclerosis and thrombosis, but also between endothelial dysfunction and both of these disease processes... - Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfacesMark A Hancock
Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 278:23260-9. 2003..The latter complex exhibits a reduced turnover number, thereby accounting for inhibition of plasminogen activation in the presence of apo(a)/Lp(a)... - Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicityMarlys L Koschinsky
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
Curr Opin Lipidol 15:167-74. 2004..Whereas many pathogenic mechanisms have been proposed for lipoprotein(a), it remains to be conclusively demonstrated which mechanisms are relevant to human disease... - Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action of an enigmatic lipoproteinMarlys L Koschinsky
Department of Biochemistry, Queen s University, A208 Botterell Hall, Kingston, ON K7L 3N6, Canada
Curr Atheroscler Rep 7:389-95. 2005..Clearly, Lp(a) is a risk factor for both atherothrombotic and purely thrombotic events; a plethora of mechanisms to explain these clinical findings has been provided by both in vitro studies as well as animal models for Lp(a)... 
Apolipoprotein(a), through its strong lysine-binding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathwayTaewoo Cho
Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 283:30503-12. 2008..Studies are ongoing to further dissect the molecular basis of these findings...- A role for apolipoprotein(a) in protection of the low-density lipoprotein component of lipoprotein(a) from copper-mediated oxidationBruce C Hill
Department of Biochemistry, Queen's University, Kingston, Ont, Canada K7L 3N6
Arch Biochem Biophys 412:186-95. 2003.... - Baboon lipoprotein(a) binds very weakly to lysine-agarose and fibrin despite the presence of a strong lysine-binding site in apolipoprotein(a) kringle IV type 10Andrea R Belczewski
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6
Biochemistry 44:555-64. 2005..We conclude that presentation of KIV(10) in the context of apo(a) lacking KV may interfere with the ability of KIV(10) to bind to substrates such as fibrin; this paradigm may also be present in other non-human primates... 
Regulation of the mouse gene encoding TAFI by TNFα: role of NFκB binding siteMathieu Garand
Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada
Cytokine 57:389-97. 2012..These results demonstrate that the unique NFκB site in the mouse CPB2 promoter is functional and mediates the upregulation of mouse CPB2 expression by TNFα via increase in NFκB translocation to the nucleus...- Acute phase mediators modulate thrombin-activable fibrinolysis inhibitor (TAFI) gene expression in HepG2 cellsMichael B Boffa
Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 278:9250-7. 2003..The GRE was capable of binding the glucocorticoid receptor, as assessed by gel mobility shift assays, and mutation of this element markedly decreased the ability of the TAFI promoter to be activated by dexamethasone... - Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3Lei Liu
Department of Biochemistry, Queen s University, Kingston, ON K7L3N6, Canada
Biochem J 418:325-36. 2009..Taken together, the results of the present study suggest that the apo(a) component of Lp(a) signals through integrin alphaVbeta3 to activate endothelial cells... - Molecular analysis of the human thrombin-activatable fibrinolysis inhibitor gene promoterMathieu Garand
Department of Biochemistry, Queen s University, Kingston, ON, Canada
Br J Haematol 138:231-44. 2007..Transient transfections of CPB2 promoter-reporter constructs showed that HNF-1alpha binding is essential for the activity of this promoter in HepG2 cells, indicating that HNF-1alpha is involved in the liver-specific expression of CPB2... - A ligand-induced conformational change in apolipoprotein(a) enhances covalent Lp(a) formationLev Becker
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 278:14074-81. 2003..Although the functions of apo(a) and plasminogen have diverged considerably, elements of structural and conformational homology have been retained leading to similar regulation of two unrelated biological processes... - Stimulation of vascular smooth muscle cell proliferation and migration by apolipoprotein(a) is dependent on inhibition of transforming growth factor-beta activation and on the presence of kringle IV type 9Caroline H O'Neil
Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 279:55187-95. 2004..The kringle IV type 9-dependent effects of apo(a) on SMC proliferation required the presence of plasminogen, suggesting for the first time that this kringle mediates the ability of apo(a) to inhibit pericellular plasmin formation... - Definition of the structural elements in plasminogen required for high-affinity binding to apolipoprotein(a): a study utilizing surface plasmon resonanceMark A Hancock
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6
Biochemistry 43:12237-48. 2004..Differential binding kinetics between Glu(1)-/Lys(78)-plasminogen and apo(a) may explain why Lp(a) is a stronger inhibitor of tPA-mediated Glu(1)-plasminogen activation compared to Lys(78)-plasminogen activation... - The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber formation and loss of cell-cell contact in cultured endothelial cellsMark Pellegrino
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 279:6526-33. 2004..We propose that the resultant increase in endothelial permeability caused by Lp(a) may help explain the atherosclerotic risk posed by elevated concentrations of this lipoprotein... - Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin-activatable fibrinolysis inhibitor: a functional analysisMichael B Boffa
Department of Biochemistry, Queen s University, Kingston, ON, Canada
Blood 111:183-9. 2008..We speculate that these SNPs, in part, contribute to variation in plasma TAFI concentrations via modulation of CPB2 gene expression through an effect on mRNA stability... - Catalysis of covalent Lp(a) assembly: evidence for an extracellular enzyme activity that enhances disulfide bond formationLev Becker
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada K7L 3N6
Biochemistry 45:9919-28. 2006.... - Quantitative evaluation of the contribution of weak lysine-binding sites present within apolipoprotein(a) kringle IV types 6-8 to lipoprotein(a) assemblyLev Becker
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 279:2679-88. 2004.... - Nuclear magnetic resonance (NMR) solution structure, dynamics, and binding properties of the kringle IV type 8 module of apolipoprotein(a)Seth Chitayat
Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
Biochemistry 46:1732-42. 2007..An additional ligand recognition site comprises a structured arginine-glycine-aspartate motif at the N terminus of the KIV8 module, which may mediate Lp(a)/apo(a)-integrin interactions... - Identification of a novel apolipoprotein(a)-related protein from the European hedgehog (Erinaceus europaeus)Andrea R Belczewski
Rm. A208 Botterell Hall, Department of Biochemistry, Queen's University, Kingston, Ont, Canada K7L 3N6
DNA Seq 14:15-23. 2003..The function of HaRP-1 remains unclear at present, but may constititute a member of the family of apo(a) proteins that functions in the regulation of lysine-dependent proteolysis... - Apolipoprotein(a) phenotype and lipoprotein(a) level predict peritoneal dialysis patient mortalityEduard A Iliescu
Queen s University, Kingston, Ontario, Canada
Perit Dial Int 22:492-9. 2002..To examine the associations between lipoprotein(a) [Lp(a)] level, apolipoprotein(a) [apo(a)] phenotype, and patient mortality in peritoneal dialysis (PD) patients... - Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal modelsMichael B Boffa
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada
Clin Biochem 37:333-43. 2004..The recent construction of transgenic apo(a) rabbits is a particularly promising development in view of the excellent utility of the rabbit as a model of advanced atherosclerosis... - A role for CCAAT/enhancer-binding protein in hepatic expression of thrombin-activable fibrinolysis inhibitorMichael B Boffa
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 277:25329-36. 2002..The identification of a functional C/EBP-binding site in the human TAFI promoter may have important implications for the regulation of expression of this gene during development and in response to inflammatory stimuli... - Comparative analyses of the lysine binding site properties of apolipoprotein(a) kringle IV types 7 and 10Mona N Rahman
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6
Biochemistry 41:1149-55. 2002.... - Apolipoprotein(a) stimulates nuclear translocation of β-catenin: a novel pathogenic mechanism for lipoprotein(a)Taewoo Cho
Department of Biochemistry, Queen s University, Kingston, ON K7L 3N6, Canada Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada
Mol Biol Cell 24:210-21. 2013..Taken together, our findings suggest a novel mechanism by which apo(a) can induce proinflammatory and proatherosclerotic effects through modulation of vascular endothelial cell function... - Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation systemLei Liu
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
PLoS ONE 8:e52287. 2013..This is the first report of a functional role for the glycosylation of apo(a) although the mechanisms underlying this observation remain to be determined in the context of angiogenesis... - Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological rolesMichael B Boffa
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada K7L 3N6
Clin Biochem 40:431-42. 2007..Although this field is in its infancy, much recent progress has been made and the available data suggest that the TAFI pathway is an intriguing new player in a variety of physiological and pathophysiological contexts... - Subclinical vitamin K deficiency in hemodialysis patientsRachel M Pilkey
Division of Nephrology, Queen s University, Kingston, Ontario, Canada
Am J Kidney Dis 49:432-9. 2007..Nondietary determinants of vitamin K status include apolipoprotein E (apoE) genotype, which may influence vitamin K transport to peripheral tissues... - Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCRMatthew B Lanktree
Robarts Research Institute, Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
J Lipid Res 50:768-72. 2009.... - Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedsideSantica M Marcovina
Department of Medicine, University of Washington, Seattle, Washington 98103, USA
Curr Opin Lipidol 14:361-6. 2003.... - The apolipoprotein(a) component of lipoprotein(a) mediates binding to laminin: contribution to selective retention of lipoprotein(a) in atherosclerotic lesionsAngela D'Angelo
Molecular Medicine Laboratory, University of Pavia, IRCCS Policlinico San Matteo, Piazzale Golgi 2, Pavia, Italy
Biochim Biophys Acta 1687:1-10. 2005..In summary, our data suggest that laminin may bind to apo(a) in the atherosclerotic intima, thus contributing to the selective retention of Lp(a) in this milieu... - Lipoprotein(a) is associated differentially with carotid stenosis, occlusion, and total plaque areaJonathan H Klein
Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
Arterioscler Thromb Vasc Biol 28:1851-6. 2008..We studied relationships of Lp(a) with carotid stenosis, occlusion, and total plaque area, distinct phenotypes of atherosclerosis that may be differentially affected by cardiovascular risk factors... - Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrinSotirios N Sotiriou
Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland 20892, USA
FASEB J 20:559-61. 2006..These observations suggest a novel mechanism for the atherogenic properties of Lp(a)... - A critical evaluation of the role of Lp(a) in cardiovascular disease: can Lp(a) be useful in risk assessment?Santica M Marcovina
Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, WA 98103, USA
Semin Vasc Med 2:335-44. 2002..Although characterization of Lp(a) in the general population is not presently justified, Lp(a) analysis in patients at risk for CHD may be warranted... - An apolipoprotein(a) peptide delays chylomicron remnant clearance and increases plasma remnant lipoproteins and atherosclerosis in vivoCecilia M Devlin
Department of Medicine, Columbia University, 630 W 168th St, New York, NY 10032, USA
Arterioscler Thromb Vasc Biol 25:1704-10. 2005..To investigate the effect of KIV(5-8) on lipoprotein metabolism and atherosclerosis in vivo, we created several independent lines of liver-targeted KIV(5-8) transgenic mice... - A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery diseaseMay M Luke
Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA
Arterioscler Thromb Vasc Biol 27:2030-6. 2007..The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD)... - Lipoprotein(a): a unique risk factor for cardiovascular diseaseErdembileg Anuurad
Department of Medicine, VA Northern California Health Care System, UCD Medical Center, University of California-Davis, 4150 V Street, Suite G400, Sacramento, CA 95817, USA
Clin Lab Med 26:751-72. 2006..Lp(a) is a risk factor for coronary artery disease, and smaller size apo(a) is associated with coronary artery disease. The physiologic role of Lp(a) is unknown... - Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directionsSantica M Marcovina
Department of Medicine, University of Washington, Northwest Lipid Research Laboratories, 2121 N 35th St, Seattle, WA 98103, USA
Clin Chem 49:1785-96. 2003..This report includes the most recent data presented by the workshop participants and the resulting practical and research recommendations... - Plasminogen binds to plasmin-modulated factor Xa by Ca(2+) - and C-terminal lysine-dependent and -independent interactionsJean E Grundy
Canadian Blood Services, R and D Department, University of British Columbia Centre for Blood Research, Department of Pathology and Laboratory Medicine, Vancouver
Thromb Haemost 97:38-44. 2007..The N-terminal 1 - 77 amino acids of Glu-Pg confer significant C-terminal lysine-independent binding, which may play a role during the initiating stages of plasminogen activation...