GDF11 does not rescue aging-related pathological hypertrophy.
GDF11 does not rescue aging-related pathological hypertrophy.
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DOI：
10.1161/circresaha.115.307527
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发表时间：
2015-11-06
影响因子：
20.1
通讯作者：
Houser SR
中科院分区：
文献类型：
--
作者：
Smith SC;Zhang X;Zhang X;Gross P;Starosta T;Mohsin S;Franti M;Gupta P;Hayes D;Myzithras M;Kahn J;Tanner J;Weldon SM;Khalil A;Guo X;Sabri A;Chen X;MacDonnell S;Houser SR
GDF 11（生长分化因子11）是转化生长因子β（TGFβ）分泌因子超家族的成员。最近的一项研究表明，随着年龄的增长，GDF 11血液水平的降低与病理性心脏肥大（PCH）有关，在老年小鼠中将GDF 11恢复到正常水平可以挽救PCH。确定GDF 11是否以及通过何种机制拯救衰老依赖性PCH。24月龄的C57 BL/6小鼠每天注射0.1mg/kg的重组（r）GDF 11或媒介物，持续28天。在体外证实了rGDF 11的生物活性。治疗后，rGDF 11水平显著增加，但对心脏重量（HW）或体重（BW）无显著影响。老年小鼠的HW/BW比与8或12周龄的动物没有差异，并且PCH标记物ANP在年轻小鼠与老年小鼠中没有差异。基线时，rGDF 11和溶剂治疗动物之间的射血分数、心室内部尺寸和间隔壁厚度没有显着差异，并且在治疗1周、2周和4周时保持不变。rGDF 11与溶剂处理的老年动物相比，肌细胞横截面积无差异。使用苯肾上腺素处理的新生大鼠心室肌细胞（NRVM）的体外研究，以探索GDF 11的推定的抗肥大作用，显示GDF 11不减少NRVM肥大，而是诱导肥大。我们的研究表明，在无病的24月龄C57 BL/6小鼠中没有与年龄相关的PCH，并且在老年小鼠中恢复GDF 11对心脏结构或功能没有影响。
GDF11 (Growth Differentiation Factor 11) is a member of the transforming growth factor β (TGFβ) super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH), and restoring GDF11 to normal levels in old mice rescued PCH. To determine if and by what mechanism GDF11 rescues aging dependent PCH. 24-month-old C57BL/6 mice were given a daily injection of either recombinant (r) GDF11 at 0.1mg/kg or vehicle for 28 days. rGDF11 bioactivity was confirmed in-vitro. After treatment, rGDF11 levels were significantly increased but there was no significant effect on either heart weight (HW) or body weight (BW). HW/BW ratios of old mice were not different from 8 or 12 week-old animals, and the PCH marker ANP was not different in young versus old mice. Ejection fraction, internal ventricular dimension, and septal wall thickness were not significantly different between rGDF11 and vehicle treated animals at baseline and remained unchanged at 1, 2 and 4 weeks of treatment. There was no difference in myocyte cross-sectional area rGDF11 versus vehicle-treated old animals. In vitro studies using phenylephrine-treated neonatal rat ventricular myocytes (NRVM), to explore the putative anti-hypertrophic effects of GDF11, showed that GDF11 did not reduce NRVM hypertrophy, but instead induced hypertrophy. Our studies show that there is no age-related PCH in disease free 24-month-old C57BL/6 mice and that restoring GDF11 in old mice has no effect on cardiac structure or function.