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The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice.

Luther, Daniel J
http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347

Abstract Details

2013, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
LUTHER, DANIEL J., Ph.D., Aug 2013 PHYSIOLOGY THE ROLE OF TYPE VI COLLAGEN IN CARDIAC REMODELING FOLLOWING MYOCARDIAL INFARCTION IN MICE (134 pp.) Director of Dissertation: J. Gary Meszaros Cardiac remodeling is a dynamic process largely propagated by cardiac fibroblasts (CFs), the critical mediators of wound repair. Following myocardial infarction (MI), this process is accelerated resulting in aberrant structural changes to the heart. Investigation into the fibrotic responses of the heart to injury have focused on collagens type I and III however, we have uncovered a novel role for type VI collagen (Col6). Here, we report the effects of the deletion of Col6 from the myocardium during post-MI wound repair and demonstrate that Col6-/- mice are resistant to ischemic injury resulting in reductions in infarct size and preserved cardiac function. To investigate potential mechanisms responsible for the cardioprotection in Col6-/- mice, we used histological approaches to assess the cardiac ECM for structural changes that may alter cardiac wound repair. Our results suggest looser formed collagen fibers and an abundance of type III collagen in the post-MI hearts of Col6-/- mice, in contrast to the abundance of type I collagen observed in WT post-MI mice. Additionally, we hypothesized that altered mitochondrial structure and function in the hearts of Col6-/- mice also presents a potential mechanism leading to protection from ischemic injury. To test this, we used electron microscopy (EM) and molecular approaches to assess mitochondria of Col6-/- post-MI mice. EMs of Col6-/- uninjured hearts illustrate normal mitochondrial morphology however, at 3 days post-MI Col6-/- mice demonstrate increased mitochondrial fusion, in contrast to increased mitochondrial swelling and fission observed in WT mice. By 14 days, Col6-/- mitochondria appear normal while WT post-MI mice have disrupted mitochondria. Western blot indicated differences in mitochondrial fusion/fission protein flux between groups at 24 hrs. post-MI. Oxygen consumption of isolated mitochondria from Col6-/- sham hearts demonstrate a reduced mitochondrial respiratory control index (RCI) compared to WT controls. Following MI the RCI of Col6-/- mice did not significantly decline, as was observed in WT post-MI mice. Together, these data indicate that Col6-/- mice are protected from ischemic injury leading to improved cardiac remodeling and function following MI, and differences in ECM structure and mitochondrial function are possible mechanism(s) underlying the unexpected cardioprotection observe in Col6-/- mice.
J. Gary Meszaros, Ph.D. (Advisor)
Ian Bratz, Ph.D. (Committee Member)
Charles Thodeti, Ph.D. (Committee Member)
Ken Rosenthal, Ph.D. (Committee Member)
Derek Damron, Ph.D. (Committee Member)
134 p.
Biomedical Research
Type VI Collagen; Myocardial Infarction; Cardiac Remodeling; Mitochondria

Recommended Citations

Citations

  • Luther, D. J. (2013). The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice. [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347

    APA Style (7th edition)

  • Luther, Daniel. The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice. 2013. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347.

    MLA Style (8th edition)

  • Luther, Daniel. "The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice." Doctoral dissertation, Kent State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347

    Chicago Manual of Style (17th edition)

kent1376067347
247
© 2013, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.