Analysis Tools
cardiovascular system
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• mice have normal systolic and diastolic blood pressure at 2, 4, and 10 months of age
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• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age
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• after treatment with dexamethasone (DEX), neonatal cardiomyocytes show significantly higher mRNA levels of hypertrophy markers (Nppa, Nppb) and direct glucocorticoid receptor targets (Fkbp5, Tsc22d3), and have a significantly larger surface area than both DEX-treated control cells and untreated cells, indicating increased glucocorticoid-induced cardiomyocyte hypertrophy
• GAS5 overexpression in neonatal cardiomyocytes significantly decreases DEX-induced expression of Nppa (and to a lesser extent of Tsc22d3) and reduces DEX-induced cardiomyocyte hypertrophy by decreasing their surface area
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• whole hearts are overtly enlarged at 10 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age
• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice
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• mice show significantly increased LV mass at 10 and 14 months of age
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• mice show significantly increased left ventricular (LV) wall thickness at 10 and 14 months of age; LV wall is also thicker than that in control Nkx2-5
• 6-wk-old mice treated with DEX for 14 days show a significantly thicker LV wall than both DEX-treated control mice and untreated mice
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• hearts show significantly decreased mRNA levels of Gas5 (growth arrest specific 5), an inhibitor of the glucocorticoid receptor, from P1 to 6 months of age
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• after treatment with a nonsense-mediated decay (NMD) inhibitor, neonatal cardiomyocytes show an even greater increase in Gas5 mRNA levels than similarly treated control cells, suggesting that SRSF4 binds GAS5 and protects it from degradation by NMD
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• mice show progressive diastolic dysfunction, as indicated by a significant and age-dependent reduction in the E/A wave ratio of mitral flow and an elevated isovolumetric relaxation time (IVRT) at 14 months of age
• however, LV ejection fraction (LVEF) and LV diastolic volume (LVVOLd) are normal from 6 to 14 months
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• mice exhibit a significant reduction in the early and late diastolic peak wave ratio (E/A wave ratio of mitral flow) at 14 months of age
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• at 6 months of age, mice exhibit a significantly higher heart rate than controls both under basal and isoproterenol-induced stress conditions
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• under isoproterenol-induced stress conditions, mice exhibit a negative J wave at 6 months of age
• J wave amplitude is also decreased under basal conditions but the difference is not statistically significant
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• under basal conditions, mice exhibit a wider QRS complex amplitude than controls at 6 months of age
• QRS amplitude is also wider under isoproterenol-induced stress conditions but the difference is not statistically significant
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• under isoproterenol-induced stress conditions, mice exhibit a significantly prolonged cQT (= QT interval corrected for heart rate) at 6 months of age
• cQT is also longer under basal conditions but the difference is not statistically significant
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• under isoproterenol-induced stress conditions, mice exhibit a significantly depressed ST-segment at 6 months of age
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• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave
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growth/size/body
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• whole hearts are overtly enlarged at 10 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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• mice show a significant increase in normalized cardiac mass and heart weight to body weight (HW/BW) ratio at 10 and 14 months of age; however, BW is normal from 6 to 14 months of age
• after 2 wks of treatment with DEX, mice show a significantly higher HW/BW ratio than both DEX-treated control mice and untreated mice
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muscle
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• cardiomyocyte cross-sectional area (CSA) is significantly increased at 2 and 4 months of age
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• mice develop LV hypertrophy with significantly increased LV wall thickness, LV mass, cardiomyocyte cross-sectional area, and mRNA levels of heart disease markers Nppb (natriuretic peptide type B, aka Bnp) and Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta)
• after 2 wks of treatment with DEX, mice show significantly higher mRNA levels of hypertrophy markers (Nppa) and glucocorticoid receptor targets (Fkbp5, Tsc22d3) than both DEX-treated control mice and untreated mice
• GAS5 overexpression via injection of AAV9-GAS5 significantly decreases LV wall thickness and partially reduces expression of Fkbp5 and Tsc22d3 at day 7 post-injection
• however, untreated mice show normal mRNA levels of fibrosis markers and no increase in cardiac fibrosis from 2 to 14 months of age; mRNA and protein expression of Nr3c1 (aka glucocorticoid receptor, GR) is similar to that in control hearts from 2 to 8 months
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homeostasis/metabolism
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• in response to isoproterenol-induced stress, 6-mo-old mice show more severe electrocardiographic features of cardiac hypertrophy and abnormal repolarization, with a further increase in the cQT interval, marked ST-segment depression, and a negative J wave
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