Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction.
Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction.
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DOI：
10.1371/journal.pone.0020369
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hartner A
中科院分区：
文献类型：
--
作者：
Menendez-Castro C;Fahlbusch F;Cordasic N;Amann K;Münzel K;Plank C;Wachtveitl R;Rascher W;Hilgers KF;Hartner A
宫内生长受限（IUGR）是日后患心血管疾病的一个危险因素。IUGR后心血管系统早期的结构和功能改变可能与其发病机制有关。我们验证了IUGR在高血压发病前会导致原发性心肌和血管改变这一假设。采用了一种孕期母体蛋白质限制的大鼠IUGR模型。母鼠被喂食低蛋白（LP；酪蛋白8.4%）或等热量正常蛋白饮食（NP；酪蛋白17.2%）。每窝子代保留6只雄性。在新生大鼠和70日龄大鼠的心肌和血管组织中进行了免疫组织化学和实时定量PCR分析。在新生IUGR大鼠的主动脉中，结缔组织生长因子（CTGF）的表达上调了3.2倍。在70日龄时，IUGR大鼠主动脉中Ⅰ型胶原蛋白的表达增加了5.6倍。在新生IUGR大鼠的心脏中，细胞增殖比对照组更为显著。在70日龄时，骨桥蛋白的表达上调了7.2倍。观察到促纤维化细胞因子转化生长因子 -β（TGF -β）和CTGF以及微纤维基质分子的表达增加了3 - 7倍。在70日龄时，与对照组相比，IUGR动物心肌中胶原蛋白的表达和沉积更为显著。在低蛋白饮食模型中，IUGR导致青春期促纤维化基因表达模式的改变以及血管和心脏的离散结构异常，但除CTGF外，并非早在出生时就出现。有创和无创血压测量证实，在所研究的时间点IUGR大鼠血压正常，且观察到的变化与血压升高无关。因此，血管壁和心肌基质成分的改变可能使IUGR动物在日后易患心血管疾病。
Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life.
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DOI：
10.1016/s0960-0760(03)00198-5
发表时间：
2003-06-01
影响因子：
4.1
作者：
Konishi, A;Tazawa, C;Sasano, H
通讯作者：
Sasano, H
影响因子：
6.5
作者：
Frazier, K;Williams, S;Grotendorst, GR
通讯作者：
Grotendorst, GR
影响因子：
37.8
作者：
Crispi, Fatima;Bijnens, Bart;Gratacos, Eduard
通讯作者：
Gratacos, Eduard
影响因子：
8.3
作者：
Alexander, BT
通讯作者：
Alexander, BT
影响因子：
3.8
作者：
Doherty, CB;Lewis, RM;Burton, GJ
通讯作者：
Burton, GJ