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Signs of diastolic dysfunction are graded by serum testosterone levels in aging C57BL/6 male mice
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2021-06-21 , DOI: 10.1016/j.mad.2021.111523
Shubham Banga 1 , Stefan D Heinze-Milne 1 , Judith Godin 2 , Susan E Howlett 3
Affiliation  

We investigated whether maladaptive, age-associated changes in heart structure and function were linked to circulating testosterone levels. Male C57BL/6 mice had a gonadectomy (GDX) or sham surgery at 4 weeks and effects of GDX on the heart were examined with echocardiography. Serum testosterone was measured with ELISA. Left ventricular (LV) mass increased with age but was smaller in GDX mice than sham at 18 months (144.0 ± 8.7 vs 118.2 ± 11.9 mg; p = 0.009). The isovolumic relaxation time (IVRT) declined with age but was prolonged in GDX mice at 18 months (10.5 ± 0.8 vs 12.5 ± 0.5 msec, p = 0.008). Ejection fraction did not change with age or GDX, but E/A ratios were lower in GDX mice than controls at 18 months (1.6 ± 0.2 vs 1.3 ± 0.1, p = 0.021). When links between serum testosterone and cardiac parameters were examined longitudinally in 18−24-month-old mice, LV mass declined with decreasing testosterone (β = 37.70, p = 0.016), however IVRT increased as testosterone decreased (β=−2.69, p = 0.036). Since longer IVRT and lower E/A ratios are signs of diastolic dysfunction, low circulating testosterone may promote or exacerbate diastolic dysfunction in older males. These findings suggest that lower testosterone directly modifies heart structure and function to promote maladaptive remodeling and diastolic dysfunction in the aging heart.



中文翻译:

舒张功能障碍的迹象由衰老 C57BL/6 雄性小鼠的血清睾酮水平分级

我们调查了心脏结构和功能中与年龄相关的不适应变化是否与循环睾酮水平有关。雄性 C57BL/6 小鼠在 4 周时进行了性腺切除术 (GDX) 或假手术,并用超声心动图检查了 GDX 对心脏的影响。用ELISA测量血清睾酮。左心室 (LV) 质量随着年龄的增长而增加,但 GDX 小鼠在 18 个月时比假小鼠更小(144.0 ± 8.7 对 118.2 ± 11.9 mg;p = 0.009)。等容弛豫时间 (IVRT) 随着年龄的增长而下降,但在 GDX 小鼠中在 18 个月时延长(10.5 ± 0.8 对 12.5 ± 0.5 毫秒,p = 0.008)。射血分数不随年龄或 GDX 而变化,但 GDX 小鼠的 E/A 比在 18 个月时低于对照组(1.6 ± 0.2 对 1.3 ± 0.1,p = 0.021)。当在 18-24 个月大的小鼠中纵向检查血清睾酮和心脏参数之间的联系时,LV 质量随着睾酮的降低而下降(β = 37.70,p = 0.016),但 IVRT 随着睾酮的降低而增加(β=-2.69,p = 0.036)。由于较长的 IVRT 和较低的 E/A 比率是舒张功能障碍的迹象,低循环睾酮可能会促进或加剧老年男性的舒张功能障碍。这些发现表明,较低的睾酮直接改变心脏结构和功能,从而促进老化心脏的适应不良重塑和舒张功能障碍。低循环睾酮可能促进或加剧老年男性的舒张功能障碍。这些发现表明,较低的睾酮直接改变心脏结构和功能,从而促进老化心脏的适应不良重塑和舒张功能障碍。低循环睾酮可能促进或加剧老年男性的舒张功能障碍。这些发现表明,较低的睾酮直接改变心脏结构和功能,从而促进老化心脏的适应不良重塑和舒张功能障碍。

更新日期:2021-06-28
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