Analysis Tools
mortality/aging
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• adult mice maintained off doxycline beyond the 3 week time point show increased mortality relative to age-matched on doxycline control mice
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cardiovascular system
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• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice
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• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy
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• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice
• however, body weight is not significantly altered at 3 weeks off doxycycline
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• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice
• DCM is more pronounced at 3 weeks off doxycycline
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• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice
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• M-mode echocardiography revealed a significant increase in the chamber cavity (left ventricular internal diameter, systolic [LVIDs] and LVID, diastolic [LVIDd]), left ventricular mass (LVM) and LVM/body weight ratio, and a marked decrease in LVEF and %FS in mice off doxycycline for 1.5 and 3 weeks relative to age-matched on doxycline control mice
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• electrophysiological analysis of native volume-sensitive chloride channels (VSOACs) in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of hypotonic-induced VSOAC currents, whereas at 1.5 weeks, VSOAC current densities are significantly reduced, relative to age-matched on doxycycline controls; no difference in current densities are noted under isotonic conditions prior to cell swelling
• membrane capacitance is significantly increased in ventricular myocytes from mice 3 weeks off doxyclycline relative to ventricular myocytes from on doxycycline control mice; however, no difference in membrane capacitance is noted in atrial myocytes at 3 weeks off doxycycline
• at 1.5 weeks off doxycycline, residual hypotonic-induced VSOAC currents are totally abolished in isolated atrial myocytes by perfusion of 100 nM PDBu (a protein kinase C activator), similar to VSOAC currents in atrial cells from on doxycycline control mice
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• at 3 weeks off doxycline, adult mice display severe signs of heart failure
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muscle
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• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy
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• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice
• DCM is more pronounced at 3 weeks off doxycycline
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• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice
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growth/size/body
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• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice
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• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy
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• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice
• however, body weight is not significantly altered at 3 weeks off doxycycline
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