Diastolic dysfunction in a pre-clinical model of diabetes is associated with changes in the cardiac non-myocyte cellular composition.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2002-
    • Subject Terms:
      Ventricular Function, Left*; Diabetes Mellitus, Experimental/*complications ; Diabetic Cardiomyopathies/*etiology ; Fibroblasts/*pathology ; Myocardium/*pathology ; Ventricular Dysfunction, Left/*etiology; Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Cardiomyopathies/metabolism ; Diabetic Cardiomyopathies/pathology ; Diabetic Cardiomyopathies/physiopathology ; Diastole ; Diet, High-Fat ; Fibroblasts/metabolism ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/pathology ; Male ; Mice ; Monocytes/metabolism ; Monocytes/pathology ; Myocardium/metabolism ; Myocytes, Smooth Muscle/metabolism ; Myocytes, Smooth Muscle/pathology ; Streptozocin ; Ventricular Dysfunction, Left/metabolism ; Ventricular Dysfunction, Left/pathology ; Ventricular Dysfunction, Left/physiopathology
    • Abstract:
      Background: Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac cellular landscape in murine diabetes to identify potential cellular protagonists in the diabetic heart.
      Methods: Diabetes was induced in male FVB/N mice by low-dose streptozotocin and a high-fat diet for 26-weeks. Cardiac function was measured by echocardiography at endpoint. Flow cytometry was performed on cardiac ventricles as well as blood, spleen, and bone-marrow at endpoint from non-diabetic and diabetic mice. To validate flow cytometry results, immunofluorescence staining was conducted on left-ventricles of age-matched mice.
      Results: Mice with diabetes exhibited hyperglycaemia and impaired glucose tolerance at endpoint. Echocardiography revealed reduced E:A and e':a' ratios in diabetic mice indicating diastolic dysfunction. Systolic function was not different between the experimental groups. Detailed examination of cardiac cellularity found resident mesenchymal cells (RMCs) were elevated as a result of diabetes, due to a marked increase in cardiac fibroblasts, while smooth muscle cells were reduced in proportion. Moreover, we found increased levels of Ly6C hi monocytes in both the heart and in the blood. Consistent with this, the proportion of bone-marrow haematopoietic stem cells were increased in diabetic mice.
      Conclusions: Murine diabetes results in distinct changes in cardiac cellularity. These changes-in particular increased levels of fibroblasts-offer a framework for understanding how cardiac cellularity changes in diabetes. The results also point to new cellular mechanisms in this context, which may further aid in development of pharmacotherapies to allay the progression of cardiomyopathy associated with diabetes.
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    • Contributed Indexing:
      Keywords: Cardiac cellularity; Diabetes; Echocardiography; Fibroblast; Flow cytometry
    • Accession Number:
      0 (Blood Glucose)
      5W494URQ81 (Streptozocin)
    • Publication Date:
      Date Created: 20210602 Date Completed: 20211101 Latest Revision: 20211101
    • Publication Date:
      20221213
    • Accession Number:
      PMC8170962
    • Accession Number:
      10.1186/s12933-021-01303-9
    • Accession Number:
      34074290