Prevalence of left ventricular (LV) systolic and diastolic dysfunction increases with aging. We previously reported that urocortin 2 (Ucn2) gene transfer increases heart function in mice with heart failure with reduced ejection fraction. Here, we test the hypotheses that (1) Ucn2 gene transfer will increase LV function in aged mice and that (2) Ucn2 gene transfer given in early life will prevent age-related LV dysfunction. Nineteen-month-old (treatment study) and 3-month-old (prevention study) mice received Ucn2 gene transfer or saline. LV function was examined 3-4 months (treatment study) or 20 months (prevention study) after Ucn2 gene transfer or saline injection. In both the treatment and prevention strategies, Ucn2 gene transfer increased ejection fraction, reduced LV volume, increased LV peak -dP/dt and peak +dP/dt, and reduced global longitudinal strain. Ucn2 gene transfer-in both treatment and prevention strategies-was associated with higher levels of LV SERCA2a protein, reduced phosphorylation of LV CaMKIIa, and reduced LV α-skeletal actin mRNA expression (reflecting reduced cardiac stress). In conclusion, Ucn2 gene transfer restores normal cardiac function in mice with age-related LV dysfunction and prevents development of LV dysfunction.

中文翻译：

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Urocortin 2基因转移改善老年小鼠的心脏功能。

左室收缩和舒张功能障碍的患病率随年龄增长而增加。我们以前曾报道过，urocortin 2（Ucn2）基因转移可增加心力衰竭小鼠的心功能，并降低射血分数。在这里，我们检验以下假设：（1）Ucn2基因转移将增加衰老小鼠的左室功能，（2）早年给予Ucn2基因转移将防止与年龄有关的左室功能障碍。19个月大（治疗研究）和3个月大（预防研究）的小鼠接受了Ucn2基因转移或生理盐水。在Ucn2基因转移或注射生理盐水后3-4个月（治疗研究）或20个月（预防研究）检查左室功能。在治疗和预防策略中，Ucn2基因转移均可增加射血分数，降低左心室容积，增加左室峰值-dP / dt和+ dP / dt峰值，并降低了整体纵向应变。在治疗和预防策略中的Ucn2基因转移与更高水平的LV SERCA2a蛋白，降低的LV CaMKIIa磷酸化以及降低的LVα-骨骼肌肌动蛋白mRNA表达有关（反映出降低的心脏压力）。总之，Ucn2基因转移可恢复与年龄相关的LV功能障碍的小鼠的正常心脏功能，并防止LV功能障碍的发展。