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In vivo Characterization Of Non-Myocyte Heterogeneity During The Postnatal Development Of The Cardiac Interstitium

Damen, Angela N
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1415625809

Abstract Details

2014, MS, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Cardiac fibrosis is a major contributing factor in heart failure, yet efforts to understand and target the cells responsible for fibrotic remodeling have often yielded conflicting or confusing results. The deposition of the fibrous matrix of the heart is generally attributed to fibroblasts, though many other cells in the cardiac interstitium likely influence matrix remodeling, including endothelial cells, smooth muscle cells, pericytes and immune cells. A better understanding of the developmental origins of these non-myocytes and their role in normal cardiac development is critical to parsing out their complex contribution to the adult disease process. Cardiac matrix deposition begins in the embryo, but it is the neonatal period (P0 to P7) in which dramatic changes occur in both the composition of the extracellular matrix as well as its relationship with the maturing myocytes and vasculature. Coincident with these changes, substantial growth and diversification occurs in the non-myocyte cell fraction. Neonatal fibroblasts, in particular, exhibit heterogeneity in their expression of typical fibroblast markers, such as Tcf21, Pdgfra, periostin and Fsp1 (Fibroblast specific protein-1). Fsp1 Cre has been used to mark fibroblast lineages in multiple adult organs; therefore, we examined the Fsp1 lineage in postnatal cardiac development. While neonatal Fsp1 lineage+ cells account for very few of the vimentin+ interstitial cell population, by P15 this lineage has greatly expanded with many cells exhibiting fibroblast-like morphology, intimately associating with Pecam+ cells in the developing microvasculature, and embedding deeply in the collagen matrix. Based upon the very low level of pHH3 labeling in postnatal non-myocytes, this expansion is not likely attributable to the proliferation of resident cells. Furthermore, Fsp1 lineage+ cells are CD45+ and are also positive for markers of activated macrophages. These data suggest a previously unappreciated infiltration of hematopoietic-derived cells during juvenile stages that differentiate to macrophages to the developing heart. This study provides an overview of postnatal heart morphogenesis as well as an in vivo characterization of the major non-myocyte cell populations.
Katherine Yutzey, Ph.D. (Committee Chair)
Burns Blaxall, Ph.D. (Committee Member)
Saulius Sumanas, Ph.D. (Committee Member)
52 p.
Developmental Biology
fibroblast; neonatal development; fibrosis; regeneration; macrophage; extracellular matrix

Recommended Citations

Citations

  • Damen, A. N. (2014). In vivo Characterization Of Non-Myocyte Heterogeneity During The Postnatal Development Of The Cardiac Interstitium [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1415625809

    APA Style (7th edition)

  • Damen, Angela. In vivo Characterization Of Non-Myocyte Heterogeneity During The Postnatal Development Of The Cardiac Interstitium. 2014. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1415625809.

    MLA Style (8th edition)

  • Damen, Angela. "In vivo Characterization Of Non-Myocyte Heterogeneity During The Postnatal Development Of The Cardiac Interstitium." Master's thesis, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1415625809

    Chicago Manual of Style (17th edition)

ucin1415625809
216
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This open access ETD is published by University of Cincinnati and OhioLINK.