ATF3 Transgenic Mice: Structural Analysis of Cardiac Myocytes

ABSTRACT: Over-expression of the activating transcription factor 3 (ATF3) in transgenic (TG) mice induces atrial enlargement. This manuscript reports anatomical and structural alterations in TG mice hearts. A statistical analysis showed that hearts of the TG mice (0.61±0.2 grams) are significantly heavier than those of non-transgenic (nTG) mice (0.16±0.03 grams) (P<0.05). The average myocyte cross-sectional area of the TG mice (172.51±72.72 μm2) was significantly larger than that of nTG mice (74.4±16.46 μm2) (P<0.05). The alterations varied greatly among individual atria, with and without visible calcification. Approximately 56 % of TG mice produced recognizable calcification in the right atrium. Moreover, very few apoptotic cells were observed. Ultrastructural studies of the enlarged atria showed 1) degeneration and degradation of cytoplasmic components and mineralization of mitochondria leading to total destruction and death of myocytes, 2) hyperchromatic-hypertrophic nuclei with various nuclear inclusions, 3) fibrosis and mineralization of the myocardial layer, and 4) thrombus, cartilage and bone formation. It is possible that cellular injury would cause energy metabolism impairment and/or sarcolemmal malformation leading to Ca++ accumulation and subsequent ultrastructural changes. Although pathogenesis of this alteration remains unclear, ATF3 could be involved in these abnormalities