Inflammatory dilated cardiomyopathy in Abcg5-deficient mice

Dennis W Wilson, Karen L. Oslund, Bonnie Lyons, Oded Foreman, Lisa Burzenski, Karen L. Svenson, Thomas H. Chase, Leonard D. Shultz

Research output: Contribution to journalArticle

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Abstract

Dilated cardiomyopathy (DCM) in A/J mice homozygous for the spontaneous thrombocytopenia and cardiomyopathy (trac) mutation results from a single base pair change in the Abcg5 gene. A similar mutation in humans causes sitosterolemia with high plant sterol levels, hypercholesterolemia, and early onset atherosclerosis. Analyses of CD3+ and Mac-3+ cells and stainable collagen in hearts showed inflammation and myocyte degeneration in A/J-trac/trac mice beginning postweaning and progressed to marked dilative and fibrosing cardiomyopathy by 140 days. Transmission electron microscopy (TEM) demonstrated myocyte vacuoles consistent with swollen endoplasmic reticulum (ER). Myocytes with cytoplasmic glycogen and irregular actinomyosin filament bundles formed mature intercalated disks with normal myocytes suggesting myocyte repair. A/J-trac/trac mice fed lifelong phytosterol-free diets did not develop cardiomyopathy. BALB/cByJ-trac/trac mice had lesser inflammatory infiltrates and later onset DCM. BALB/cByJ-trac/trac mice changed from normal to phytosterol-free diets had lesser T cell infiltrates but persistent monocyte infiltrates and equivalent fibrosis to mice on normal diets. B- and T-cell-deficient BALB/cBy-Rag1null trac/trac mice fed normal diets did not develop inflammatory infiltrates or DCM. We conclude that the trac/trac mouse has many features of inflammatory DCM and that the reversibility of myocardial T cell infiltration provides a novel model for investigating the progression of myocardial fibrosis.

Original languageEnglish (US)
Pages (from-to)880-892
Number of pages13
JournalToxicologic Pathology
Volume41
Issue number6
DOIs
StatePublished - Aug 2013

Fingerprint

Dilated Cardiomyopathy
Nutrition
Cardiomyopathies
Phytosterols
T-cells
Thrombocytopenia
Muscle Cells
Glycogen
Infiltration
Repair
Collagen
Genes
Diet
Transmission electron microscopy
T-Lymphocytes
Fibrosis
Mutation
Vacuoles
Hypercholesterolemia
Transmission Electron Microscopy

Keywords

  • animal models
  • cardiomyopathy
  • cardiovascular system
  • electron microscopy
  • immunopathology
  • nutrition/food products

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Cell Biology
  • Molecular Biology

Cite this

Wilson, D. W., Oslund, K. L., Lyons, B., Foreman, O., Burzenski, L., Svenson, K. L., ... Shultz, L. D. (2013). Inflammatory dilated cardiomyopathy in Abcg5-deficient mice. Toxicologic Pathology, 41(6), 880-892. https://doi.org/10.1177/0192623312466191

Inflammatory dilated cardiomyopathy in Abcg5-deficient mice. / Wilson, Dennis W; Oslund, Karen L.; Lyons, Bonnie; Foreman, Oded; Burzenski, Lisa; Svenson, Karen L.; Chase, Thomas H.; Shultz, Leonard D.

In: Toxicologic Pathology, Vol. 41, No. 6, 08.2013, p. 880-892.

Research output: Contribution to journalArticle

Wilson, DW, Oslund, KL, Lyons, B, Foreman, O, Burzenski, L, Svenson, KL, Chase, TH & Shultz, LD 2013, 'Inflammatory dilated cardiomyopathy in Abcg5-deficient mice', Toxicologic Pathology, vol. 41, no. 6, pp. 880-892. https://doi.org/10.1177/0192623312466191
Wilson DW, Oslund KL, Lyons B, Foreman O, Burzenski L, Svenson KL et al. Inflammatory dilated cardiomyopathy in Abcg5-deficient mice. Toxicologic Pathology. 2013 Aug;41(6):880-892. https://doi.org/10.1177/0192623312466191
Wilson, Dennis W ; Oslund, Karen L. ; Lyons, Bonnie ; Foreman, Oded ; Burzenski, Lisa ; Svenson, Karen L. ; Chase, Thomas H. ; Shultz, Leonard D. / Inflammatory dilated cardiomyopathy in Abcg5-deficient mice. In: Toxicologic Pathology. 2013 ; Vol. 41, No. 6. pp. 880-892.
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