雄性Ts65Dn小鼠衰老后的心脏功能保留,但大小和烟酰胺腺嘌呤二核苷酸信号通路发生改变。

IF 2.2 3区 医学 Q3 PHYSIOLOGY
Josef Brandauer, Candace N Receno, Cynthia Anyaoku, Lauren E Cooke, Hannalyn M Schwarzer, Keith C DeRuisseau, Caitlin M Cunningham, Lara R DeRuisseau
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引用次数: 0

摘要

唐氏综合征(Ds)与出生时的先天性心脏缺陷有关,但老年时的心脏功能尚未得到评估。我们使用Ds模型Ts65Dn小鼠,用超声心动图量化18月龄雄性Ts65Dn小鼠和WT小鼠的心脏结构和功能。我们研究了心脏重量、烟酰胺腺嘌呤二核苷酸(NAD)信号和线粒体(柠檬酸合成酶)活性,因为这些途径可能与Ds的心脏病理有关。与WT相比,Ts65Dn组左心室体积更小,两次舒张期左心室前壁厚度(LVAW_d;mm)和收缩期(LVAW_s;Mm),超声心动图评估。其他功能指标组间相似,包括左室收缩期末期面积(mm2)、左室舒张末期面积(mm2)、左室收缩期末期直径(mm)、左室舒张末期直径(mm)、等容松弛时间(ms)、二尖瓣心房峰值速度(mm/s)、二尖瓣早期峰值速度(mm/s)、心房与早期峰值速度之比(E/A)、心率(bpm)、射血分数(%)和缩短分数(%)。与WT小鼠相比,Ts65Dn小鼠左心室烟酰胺磷酸核糖基转移酶(NAMPT)蛋白表达、NAD浓度和组织重量均较低。各组间Sirtuin 3 (SIRT3)蛋白表达及柠檬酸合成酶活性无显著差异。虽然男性Ts65Dn患者的心脏功能一般保持不变,但心脏大小的改变和生物能量紊乱可能导致Ds患者的衰老差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

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来源期刊
CiteScore
5.30
自引率
3.60%
发文量
145
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology publishes original investigations that illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. Major areas of emphasis include regulation in genetically modified animals; model organisms; development and tissue plasticity; neurohumoral control of circulation and hypertension; local control of circulation; cardiac and renal integration; thirst and volume, electrolyte homeostasis; glucose homeostasis and energy balance; appetite and obesity; inflammation and cytokines; integrative physiology of pregnancy-parturition-lactation; and thermoregulation and adaptations to exercise and environmental stress.
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