Elizabeth S Clark1, Victoria K Pepper2, Cameron A Best3, Ekene A Onwuka4, Tai Yi3, Shuhei Tara3, Rachel Cianciolo5, Peter Baker6, Toshiharu Shinoka7, Christopher K Breuer8. 1. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA. 2. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatric Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205-2664, USA. 3. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. 4. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Surgery, The Ohio State University, 395 W. 12th Avenue - Suite 670, Columbus, OH 43210, USA. 5. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA. 6. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pathology, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205-2664, USA. 7. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Cardiovascular Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205-2664, USA. 8. Tissue Engineering Program, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatric Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205-2664, USA. Electronic address: christopher.breuer@nationwidechildrens.org.
Abstract
BACKGROUND: Endocardial fibroelastosis (EFE) is a pathologic condition of abnormal deposition of collagen and elastin within the endocardium of the heart. It is seen in conjunction with a variety of diseases including hypoplastic left heart syndrome and viral endocarditis. While an experimental model using heterotopic heart transplant in rats has been described, we sought to fully describe a mouse model that can be used to further elucidate the potential mechanisms of and treatments for EFE. MATERIALS AND METHODS: The hearts of 2-day-old C57BL/6 mice were transplanted into the abdomen of 7-week-old C57BL/6 mice. At 2 weeks, the hearts were harvested and histologic analysis was performed using hematoxylin and eosin, Masson's trichrome, Russell-Movat's pentachrome, Picrosirius red, Hart's, Verhoeff-Van Gieson, and Weigert's Resorcin-Fuchsin stains. Additionally, one heart was analyzed using transmission electron microscopy (TEM). RESULTS: Specimens demonstrated abnormal accumulation of both collagen and elastin within the endocardium with occasional expansion into the myocardium. Heterogeneity in extracellular matrix deposition was noted in the histologic specimens. In addition, TEM demonstrated the presence of excess collagen within the endocardium. CONCLUSIONS: The heterotopic transplantation of an immature heart into a mouse results in changes consistent with EFE. This model is appropriate to investigate the etiology and treatment of EFE.
BACKGROUND:Endocardial fibroelastosis (EFE) is a pathologic condition of abnormal deposition of collagen and elastin within the endocardium of the heart. It is seen in conjunction with a variety of diseases including hypoplastic left heart syndrome and viral endocarditis. While an experimental model using heterotopic heart transplant in rats has been described, we sought to fully describe a mouse model that can be used to further elucidate the potential mechanisms of and treatments for EFE. MATERIALS AND METHODS: The hearts of 2-day-old C57BL/6 mice were transplanted into the abdomen of 7-week-old C57BL/6 mice. At 2 weeks, the hearts were harvested and histologic analysis was performed using hematoxylin and eosin, Masson's trichrome, Russell-Movat's pentachrome, Picrosirius red, Hart's, Verhoeff-Van Gieson, and Weigert's Resorcin-Fuchsin stains. Additionally, one heart was analyzed using transmission electron microscopy (TEM). RESULTS: Specimens demonstrated abnormal accumulation of both collagen and elastin within the endocardium with occasional expansion into the myocardium. Heterogeneity in extracellular matrix deposition was noted in the histologic specimens. In addition, TEM demonstrated the presence of excess collagen within the endocardium. CONCLUSIONS: The heterotopic transplantation of an immature heart into a mouse results in changes consistent with EFE. This model is appropriate to investigate the etiology and treatment of EFE.
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