Marlys L Koschinsky

Summary

Affiliation: Queen's University
Country: Canada

Publications

  1. ncbi 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) formation
    Lev Becker
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada, K7L 3N6
    Biochemistry 43:9978-88. 2004
  2. ncbi 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
  3. ncbi Analysis of the mechanism of lipoprotein(a) assembly
    M L Koschinsky
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
    Clin Genet 52:338-46. 1997
  4. ncbi Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action of an enigmatic lipoprotein
    Marlys L Koschinsky
    Department of Biochemistry, Queen s University, A208 Botterell Hall, Kingston, ON K7L 3N6, Canada
    Curr Atheroscler Rep 7:389-95. 2005
  5. ncbi Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity
    Marlys L Koschinsky
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
    Curr Opin Lipidol 15:167-74. 2004
  6. ncbi Lipoprotein(a) and the link between atherosclerosis and thrombosis
    Marlys L Koschinsky
    Department of Biochemistry, Queen s University, Kingston, Ontario
    Can J Cardiol 20:37B-43B. 2004
  7. ncbi Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfaces
    Mark A Hancock
    Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
    J Biol Chem 278:23260-9. 2003
  8. pmc 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 pathway
    Taewoo Cho
    Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
    J Biol Chem 283:30503-12. 2008
  9. ncbi A role for apolipoprotein(a) in protection of the low-density lipoprotein component of lipoprotein(a) from copper-mediated oxidation
    Bruce C Hill
    Department of Biochemistry, Queen s University, Kingston, Ont, Canada K7L 3N6
    Arch Biochem Biophys 412:186-95. 2003
  10. ncbi 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 10
    Andrea R Belczewski
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada K7L 3N6
    Biochemistry 44:555-64. 2005

Collaborators

Detail Information

Publications44

  1. ncbi 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) formation
    Lev Becker
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada, K7L 3N6
    Biochemistry 43:9978-88. 2004
    ....
  2. ncbi 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...
  3. ncbi Analysis of the mechanism of lipoprotein(a) assembly
    M L Koschinsky
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
    Clin Genet 52:338-46. 1997
    ....
  4. ncbi Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action of an enigmatic lipoprotein
    Marlys 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)...
  5. ncbi Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity
    Marlys 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...
  6. ncbi Lipoprotein(a) and the link between atherosclerosis and thrombosis
    Marlys 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...
  7. ncbi Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfaces
    Mark 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)...
  8. pmc 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 pathway
    Taewoo 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...
  9. ncbi A role for apolipoprotein(a) in protection of the low-density lipoprotein component of lipoprotein(a) from copper-mediated oxidation
    Bruce C Hill
    Department of Biochemistry, Queen s University, Kingston, Ont, Canada K7L 3N6
    Arch Biochem Biophys 412:186-95. 2003
    ....
  10. ncbi 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 10
    Andrea 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...
  11. pmc 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, 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...
  12. doi Regulation of the mouse gene encoding TAFI by TNFα: role of NFκB binding site
    Mathieu 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...
  13. ncbi Acute phase mediators modulate thrombin-activable fibrinolysis inhibitor (TAFI) gene expression in HepG2 cells
    Michael 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...
  14. ncbi Definition of the structural elements in plasminogen required for high-affinity binding to apolipoprotein(a): a study utilizing surface plasmon resonance
    Mark 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...
  15. doi Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3
    Lei 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...
  16. ncbi 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 9
    Caroline 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...
  17. ncbi Molecular analysis of the human thrombin-activatable fibrinolysis inhibitor gene promoter
    Mathieu 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...
  18. ncbi A ligand-induced conformational change in apolipoprotein(a) enhances covalent Lp(a) formation
    Lev 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...
  19. doi Regulation of the gene encoding human thrombin-activatable fibrinolysis inhibitor by estrogen and progesterone
    Mathieu Garand
    Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada
    Blood Coagul Fibrinolysis 24:393-404. 2013
    ..Our findings provide the molecular explanation for the ability of female sex steroids to decrease plasma TAFI concentrations...
  20. ncbi The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber formation and loss of cell-cell contact in cultured endothelial cells
    Mark 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...
  21. pmc Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system
    Lei 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...
  22. ncbi Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin-activatable fibrinolysis inhibitor: a functional analysis
    Michael 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...
  23. ncbi Catalysis of covalent Lp(a) assembly: evidence for an extracellular enzyme activity that enhances disulfide bond formation
    Lev Becker
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada K7L 3N6
    Biochemistry 45:9919-28. 2006
    ....
  24. ncbi 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...
  25. ncbi 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...
  26. ncbi Quantitative evaluation of the contribution of weak lysine-binding sites present within apolipoprotein(a) kringle IV types 6-8 to lipoprotein(a) assembly
    Lev Becker
    Department of Biochemistry, Queen s University, Kingston, Ontario K7L 3N6, Canada
    J Biol Chem 279:2679-88. 2004
    ....
  27. ncbi Apolipoprotein(a) phenotype and lipoprotein(a) level predict peritoneal dialysis patient mortality
    Eduard 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...
  28. ncbi Screening for and management of elevated Lp(a)
    Michael B Boffa
    Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, Canada
    Curr Cardiol Rep 15:417. 2013
    ....
  29. ncbi A role for CCAAT/enhancer-binding protein in hepatic expression of thrombin-activable fibrinolysis inhibitor
    Michael 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...
  30. ncbi Comparative analyses of the lysine binding site properties of apolipoprotein(a) kringle IV types 7 and 10
    Mona N Rahman
    Department of Biochemistry, Queen s University, Kingston, Ontario, Canada K7L 3N6
    Biochemistry 41:1149-55. 2002
    ....
  31. ncbi Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models
    Michael 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...
  32. pmc Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR
    Matthew 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
    ....
  33. ncbi Subclinical vitamin K deficiency in hemodialysis patients
    Rachel 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...
  34. ncbi Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles
    Michael 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...
  35. ncbi The apolipoprotein(a) component of lipoprotein(a) mediates binding to laminin: contribution to selective retention of lipoprotein(a) in atherosclerotic lesions
    Angela 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...
  36. ncbi Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin
    Sotirios 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)...
  37. ncbi Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside
    Santica M Marcovina
    Department of Medicine, University of Washington, Seattle, Washington 98103, USA
    Curr Opin Lipidol 14:361-6. 2003
    ....
  38. doi Lipoprotein(a) is associated differentially with carotid stenosis, occlusion, and total plaque area
    Jonathan 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...
  39. ncbi Plasminogen binds to plasmin-modulated factor Xa by Ca(2+) - and C-terminal lysine-dependent and -independent interactions
    Jean 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...
  40. ncbi 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...
  41. ncbi Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions
    Santica 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...
  42. ncbi An apolipoprotein(a) peptide delays chylomicron remnant clearance and increases plasma remnant lipoproteins and atherosclerosis in vivo
    Cecilia 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...
  43. ncbi A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease
    May 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)...
  44. ncbi Lipoprotein(a): a unique risk factor for cardiovascular disease
    Erdembileg 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...