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Prakash Arumugam Dissertation.pdf (12.16 MB)

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The Role of Interleukin-2 in Directing Vascular Smooth Muscle Cell Function and its Implications for Understanding the Progression of Atherosclerosis

Arumugam, Prakash
http://rave.ohiolink.edu/etdc/view?acc_num=wright1472497033

Abstract Details

2016, Doctor of Philosophy (PhD), Wright State University, Biomedical Sciences PhD.
Atherosclerosis is an inflammatory disorder of the vasculature leading to the development of plaques within vessel walls. A critical component of atherosclerosis involves migration and proliferation of vascular smooth muscle cells (VSMCs) into the developing plaque, however, its mechanism is not yet understood. Previous studies have reported that IL-2 is deposited within the vasculature and IL-2 accumulates within atherosclerotic plaques due to secretion by infiltrating Th-1 cells. A limited number of studies suggest that VSMCs express a partial IL-2 receptor, comprising the ß and ¿ subunit. This suggests that IL-2 may elicit a physiological response in VSMCs. Considering IL-2’s proliferative function among cells of the immune system, we hypothesized that VSMCs respond to IL-2 by proliferation and migration in vitro. Since the IL-2 receptor has the highest affinity as a heterotrimeric protein comprised of a, ß, and ¿ subunits, it is likely that VSMCs also express the IL-2 receptor a subunit. We observed a pronounced increase of DNA synthesis in IL-2 treated VSMCs by using the CLICK-IT assay. Using the Boyden Chamber assay, we showed that IL-2 caused significant VSMC migration. IL-2R a mRNA was detected in VSMCs by RT-PCR using intron-spanning primers and confirmed by sequencing. IL-2 receptor a protein of the expected molecular weight was observed in VSMC lysates by western blot analysis using a protein specific antibody. Additional studies using immunofluorescence and cell-fractionation revealed that IL2R a subunit localizes to the nuclear envelope of VSMCs. Finally, we have found IL-2 activates the MAPK and PI3K/AKT signaling pathways within VSMCs. Expression of the tripartite IL-2 receptor (a, ß, ¿) within VSMCs is a novel observation. Working through this receptor IL-2 may induce proliferation and migration of VSMC’s into sites of developing plaques thereby contributing to the pathogenesis of atherosclerosis.
Lucile Wrenshall, M.D., Ph.D. (Advisor)
James Olson, Ph.D. (Committee Member)
Mark Rich, M.D., Ph.D. (Committee Member)
Jeffrey Travers, M.D., Ph.D. (Committee Member)
David Cool, Ph.D. (Committee Member)
119 p.
Biomedical Research
biomedical

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Citations

  • Arumugam, P. (2016). The Role of Interleukin-2 in Directing Vascular Smooth Muscle Cell Function and its Implications for Understanding the Progression of Atherosclerosis [Doctoral dissertation, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1472497033

    APA Style (7th edition)

  • Arumugam, Prakash. The Role of Interleukin-2 in Directing Vascular Smooth Muscle Cell Function and its Implications for Understanding the Progression of Atherosclerosis. 2016. Wright State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1472497033.

    MLA Style (8th edition)

  • Arumugam, Prakash. "The Role of Interleukin-2 in Directing Vascular Smooth Muscle Cell Function and its Implications for Understanding the Progression of Atherosclerosis." Doctoral dissertation, Wright State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1472497033

    Chicago Manual of Style (17th edition)

wright1472497033
380
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This open access ETD is published by Wright State University and OhioLINK.