Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload
Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload
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DOI：
10.1152/ajpheart.01236.2006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Scherrer-Crosbie, Marielle
中科院分区：
文献类型：
--
作者：
Buys, Emmanuel S.;Raher, Michael J.;Scherrer-Crosbie, Marielle
虽然一氧化氮合酶（NOS）3是一个重要的调制器的左心室（LV）重塑，其作用在心脏反应慢性压力超负荷是有争议的。我们研究了选择性恢复NOS3-缺陷小鼠的心脏NOS3是否会调节左室重构对横主动脉缩窄（TAC）的反应。在基线时和TAC后比较NOS3缺陷（NOS3（-/-））小鼠和携带特异性指导心肌细胞中NOS3表达的转基因的NOS3（-/-）小鼠（NOS3（-/-TG）小鼠）的LV结构和功能。在基线时，超声心动图评估的左心室尺寸和功能，侵入性血流动力学测量，左心室质量和心肌细胞宽度没有差异的两种基因型。TAC后4周，超声心动图和左室收缩功能的血流动力学指标表明，NOS3（-/-TG）小鼠的收缩性能比NOS3（-/-）小鼠更好地保留。NOS3（-/-）小鼠的超声心动图左室壁厚度和心肌细胞宽度大于NOS3（-/-TG）小鼠。这些基因型之间TAC诱导的心脏纤维化没有差异。TAC可增加NOS3（-/-TG）小鼠心肌超氧化物的生成，但对NOS3（-/-）小鼠无影响。在NOS3（-/-TG）小鼠中，TAC前后NOS3二聚体与单体的比率没有差异。NOS3缺陷小鼠心脏恢复NOS3可减轻TAC后左室肥大和功能障碍，表明NOS3可防止长时间压力超负荷诱导的左室重构。
Although nitric oxide synthase (NOS) 3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3(-/-)) mice and NOS3(-/-) mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3(-/-TG) mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3(-/-TG) mice than in NOS3(-/-) mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3(-/-) mice than in NOS3(-/-TG) mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3(-/-TG) but not NOS3(-/-) mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3(-/-TG) mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload.