Journal of cardiac failure · 2007
Hypertrophy and heart failure in mice overexpressing the cardiac sodium-calcium exchanger.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Roos Kenneth P, Jordan Maria C, Fishbein Michael C, Ritter Matthew R, Friedlander Martin, Chang Helen C, Rahgozar Paymon, Han Tieyan, Garcia Alejandro J, Maclellan W Robb, Ross Robert S, Philipson Kenneth D
Аннотация
BACKGROUND: The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Because heart failure is associated with increased expression of NCX1, heterozygous (HET) and homozygous (HOM) transgenic mice overexpressing NCX1 were developed and evaluated.
METHODS AND RESULTS: The NCX1 transgenic mice display 2.3-fold (HET) and 3.1-fold (HOM) increases in exchanger activity from wild-type (WT) mice. Functional information was obtained by echocardiography and catheterizations before and after hemodynamic stress from pregnancy, treadmill exercise or transaortic constriction (TAC). HET and HOM mice exhibited hypertrophy and blunted responses with beta-adrenergic stimulation. Postpartum mice from all groups were hypertrophied, but only the HOM mice exhibited premature death from heart failure. HOM mice became exercise intolerant after 6 weeks of daily treadmill running. After 21 days TAC, HET, and HOM mice exhibited significant contractile dysfunction and 15% to 40% mortality with clinical evidence of heart failure.
CONCLUSIONS: Hemodynamic stress results in a compensated hypertrophy in WT mice, but NCX1 transgenic mice exhibit decreased contractile function and heart failure in proportion to their level of NCX1 expression. Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress.
METHODS AND RESULTS: The NCX1 transgenic mice display 2.3-fold (HET) and 3.1-fold (HOM) increases in exchanger activity from wild-type (WT) mice. Functional information was obtained by echocardiography and catheterizations before and after hemodynamic stress from pregnancy, treadmill exercise or transaortic constriction (TAC). HET and HOM mice exhibited hypertrophy and blunted responses with beta-adrenergic stimulation. Postpartum mice from all groups were hypertrophied, but only the HOM mice exhibited premature death from heart failure. HOM mice became exercise intolerant after 6 weeks of daily treadmill running. After 21 days TAC, HET, and HOM mice exhibited significant contractile dysfunction and 15% to 40% mortality with clinical evidence of heart failure.
CONCLUSIONS: Hemodynamic stress results in a compensated hypertrophy in WT mice, but NCX1 transgenic mice exhibit decreased contractile function and heart failure in proportion to their level of NCX1 expression. Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress.