Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring:: Possible involvement of local cardiac angiotensin system in developmental origins of cardiovascular disease
Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring:: Possible involvement of local cardiac angiotensin system in developmental origins of cardiovascular disease
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DOI：
10.1210/en.2006-0706
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Sagawa, Norimasa
中科院分区：
文献类型：
--
作者：
Kawamura, Makoto;Itoh, Hiroaki;Sagawa, Norimasa
有证据表明，子宫内营养不良以及遗传和环境因素是成年期心血管疾病的危险因素。最近，血管紧张素原和相关生物活性物质的局部表达已被证明在心脏重塑（即纤维化和肥厚）中发挥关键作用。本研究的目的是阐明局部心脏血管紧张素系统可能参与胎儿营养不良引起的心血管疾病。我们开发了一种因母体食物限制而导致子宫内营养不良的小鼠模型，其中后代（UN后代）表现出收缩压升高（8周龄，P < 0.05；16周，P < 0.01）、冠状动脉血管周围纤维化（16周，P < 0.05）和心脏肥大（16周，P < 0.01），心肌细胞增大，同时血管紧张素原 (P < 0.05) 和内皮素-1 (P < 0.01) mRNA 表达显着增加，左心室血管紧张素 II 和内皮素-1 免疫染色呈增加趋势（16 周）。这些发现表明，胎儿营养不良激活了局部心脏血管紧张素系统相关的生物活性物质，这至少部分地促进了晚年心脏重塑的发展，与血压升高的影响相一致。
Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring ( UN offspring) showed an increase in systolic blood pressure ( 8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery ( 16 wk, P < 0.05) and cardiac cardiomegaly ( 16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen ( P < 0.05) and endothelin-1 ( P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles ( 16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.