Marjorie E Zettler

Publications (5)13.87 Total impact

• Article: Augmented cell cycle protein expression and kinase activity in atherosclerotic rabbit vessels.

  Marjorie E Zettler, Michele A Merchant, Grant N Pierce
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  ABSTRACT: Cell proliferation within a primary atherosclerotic plaque is controversial. Identifying changes in cell cycle protein expression and the activities of their related kinases would provide valuable evidence of mitotic activity in the atherosclerotic lesion. Oxidized low-density lipoprotein has been shown to induce a significant increase in the total number of rabbit vascular smooth muscle cells in culture. In the present study, whole aortic cell extracts were harvested from rabbits fed a cholesterol-supplemented diet for eight weeks to induce modest plaque development, or 16 weeks to induce later, more severe plaque progression. Expression levels of cyclin A, cyclin-dependent kinase 4 (Cdk 4) and proliferating cell nuclear antigen were measured, as well as the activities of Cdk 4, Cdk 2 and Cdk 1. At both time points, the expression levels of cyclin A, Cdk 4 and proliferating cell nuclear antigen were significantly elevated. The activity of all three Cdks was also increased. There were no significant differences between moderate and more severe atherosclerosis. Surprisingly, tissues that neighboured the plaques, but did not show visible plaque formation on the vessel surface, also had significantly elevated cyclin A expression levels, but not as high as in the plaque areas. In conclusion, the primary atherosclerotic plaque exhibited elevated mitotic activity as shown by increased expression levels and activities of several cell cycle proteins. Expression levels were similar during moderate and severe atherosclerosis, and were even detected in nonatherosclerotic vascular tissue bordering the plaque.
  Experimental and clinical cardiology 01/2010; 15(4):e139-44. · 0.58 Impact Factor
• Article: A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers.

  Nalini Kaul, Renee Kreml, J Alejandro Austria, Melanie N Richard, Andrea L Edel, Elena Dibrov, Satoru Hirono, Marjorie E Zettler, Grant N Pierce
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  ABSTRACT: The impact of dietary polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 series on the cardiovascular system is well documented. To directly compare the effects of three dietary oils (fish, flaxseed and hempseed) given in concentrations expected to be self-administered in the general population on specific cardiovascular parameters in healthy volunteers. 86 healthy male and female volunteers completed a 12 week double blinded, placebo controlled, clinical trial. They were randomly assigned to one of the four groups. Subjects were orally supplemented with two 1 gm capsules of placebo, fish oil, flaxseed oil or hempseed oil per day for 12 weeks. Plasma levels of the n-3 fatty acids docosahexanoic acid and eicosapentanoic acid increased after 3 months supplementation with fish oil. Alpha linolenic acid concentrations increased transiently after flaxseed supplementation. However, supplementation with hempseed oil did not significantly alter the concentration of any plasma fatty acid. The lipid parameters (TC, HDL-C, LDL-C and TG) did not show any significant differences among the four groups. Oxidative modification of LDL showed no increase in lag time over the 12 wk period. None of the dietary interventions induced any significant change in collagen or thrombin stimulated platelet aggregation and no increase in the level of inflammatory markers was observed. From a consumer's perspective, ingesting 2 capsules of any of these oils in an attempt to achieve cardiovascular health benefits may not provide the desired or expected result over a 3 month period.
  Journal of the American College of Nutrition 03/2008; 27(1):51-8. · 2.29 Impact Factor
• Article: Oxidized low-density lipoprotein retards the growth of proliferating cells by inhibiting nuclear translocation of cell cycle proteins.

  Marjorie E Zettler, Michele A Prociuk, J Alejandro Austria, Guangming Zhong, Grant N Pierce
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  ABSTRACT: Our study tested the hypothesis that the mitogenic effect of oxidized low-density lipoprotein (oxLDL) on vascular cells may be further enhanced by the presence of cytokines and growth factors known to be present in the atherosclerotic environment. Quiescent fibroblasts and vascular smooth muscle cells were treated with 10 or 50 microg/mL minimally-oxidized LDL in combination with serum for 24 or 48 hours. Surprisingly, these cells showed inhibited release from growth arrest and a significant reduction in the number of cells completing the cell cycle when compared with cells treated with serum alone. This was not due to an induction of apoptosis. The antiproliferative effects were not closely associated with changes in the expression of cell cycle proteins. Instead, oxLDL inhibited the translocation of cell cycle proteins cell division cycle (Cdc) 2, cyclin-dependent kinase (Cdk) 2, Cdk 4, Cyclin A, Cyclin B1, Cyclin D1, and proliferative cell nuclear antigen (PCNA) into the nucleus, as compared with separate treatments with serum alone. Kinase activation associated with specific cell cycle proteins was also inhibited by oxLDL. oxLDL, in the presence of serum, has a surprising inhibitory effect on cell proliferation that occurs through an inhibition of import of cell cycle proteins into the cell nucleus.
  Arteriosclerosis Thrombosis and Vascular Biology 05/2004; 24(4):727-32. · 6.37 Impact Factor
• Article: OxLDL stimulates cell proliferation through a general induction of cell cycle proteins.

  Marjorie E Zettler, Michele A Prociuk, J Alejandro Austria, Hamid Massaeli, Guangming Zhong, Grant N Pierce
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  ABSTRACT: Oxidized low-density lipoprotein (oxLDL) may be involved in atherosclerosis by stimulating proliferation of cells in the vessel wall. The purpose of this study was to identify the mechanism by which oxLDL induces proliferation. Quiescent human fibroblasts and rabbit smooth muscle cells were treated with 0, 10, or 50 microg/ml oxLDL for 24-48 h. This resulted in significant increases in total cell counts at both concentrations of oxLDL, at both time points, for both types of cells. Western blot analysis revealed that oxLDL-stimulated cell proliferation was associated with significant increases in the expression of proteins that regulate entry into and progression through the cell cycle [cell division cycle 2, cyclin-dependent kinase (cdk) 2, cdk 4, cyclin B1, cyclin D1, and PCNA]. Surprisingly, the expression of cell cycle inhibitors (p21 and p27) was stimulated by oxLDL as well, but this was to a lesser extent than the effects on cell cycle-activating proteins. OxLDL also induced nuclear localization of all cell cycle proteins examined. The similar effects of oxLDL on the translocation and expression of both cell cycle-activating and -inhibiting proteins may explain the controlled proliferative phenomenon observed in atherosclerosis as opposed to the more rapid proliferative event characteristic of cancer.
  AJP Heart and Circulatory Physiology 03/2003; 284(2):H644-53. · 3.71 Impact Factor
• Article: Cell Cycle Proteins and Atherosclerosis

  Marjorie E. Zettler, Grant N. Pierce
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  ABSTRACT: Progression of the eukaryotic cell through the cell cycle to induce cell proliferation is a fundamental event in developmental growth processes. Specific cell cycle proteins are critical for either inducing or suppressing the cell cycle. These proteins, therefore, have been found to be key players in regulating cell proliferation in diseases like cancer and atherosclerosis. The present manuscript reviews the process of cell proliferation in atherosclerosis and the data that have implicated the various cell cycle proteins in restenotic and atherosclerotic vascular disease. Zusammenfassung Ein fundamentaler Vorgang bei Wachstumsprozessen eukaryonter Zellen ist das Durchlaufen des Zellzyklus bei der Zellproliferation. Spezifische Zellzyklusproteine sind eintscheidend, um entweder den Zellzyklus zu beginnen oder zu beenden. Diese Proteine haben daher eine Schlsselrolle bei der Regulation der Zellproliferation, vor allem bei Erkrankungen wie Krebs und Atherosklerose. Es wird die Zellproliferation bei der Atherosklerose beschrieben und auf die Bedeutung verschiedener Zellzyklusproteine bei einer Restenose und atherosklerotischen Geferkrankungen eingegangen.
  Herz 04/2000; 25(2):100-107. · 0.92 Impact Factor