Dissertation/Thesis Abstract

The role of type VI collagen in cardiac remodeling following myocardial infarction in mice
by Luther, Daniel J., Ph.D., Kent State University, 2013, 150; 3618869
Abstract (Summary)

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.

Indexing (document details)
Advisor: Meszaros, J. Gary
Commitee: Bratz, Ian, Damron, Derek, Rosenthal, Ken, Thodeti, Charles
School: Kent State University
Department: Biological Sciences
School Location: United States -- Ohio
Source: DAI-B 75/08(E), Dissertation Abstracts International
Subjects: Biomedical engineering
Keywords: Cardiac remodeling, Mitochondria, Myocardial infarction, Type VI collagen
Publication Number: 3618869
ISBN: 9781303873966
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