Systemic maternal inflammation and neonatal hyperoxia induces remodeling and left ventricular dysfunction in mice.
Systemic maternal inflammation and neonatal hyperoxia induces remodeling and left ventricular dysfunction in mice.
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DOI：
10.1371/journal.pone.0024544
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rogers LK
中科院分区：
文献类型：
--
作者：
Velten M;Hutchinson KR;Gorr MW;Wold LE;Lucchesi PA;Rogers LK
新生儿环境对成人心血管疾病发展的影响尚不清楚。母体全身性炎症与发育中的胎儿生长迟缓、早产和成熟缺陷有关。通常早产儿或小胎龄婴儿需要医疗干预，如氧气治疗。医学干预对不成熟生理的长期病理后果尚不清楚。在本研究中，我们假设母体全身性炎症和新生儿高氧暴露损害心脏结构，导致成年期左室功能障碍。妊娠C3H/HeN小鼠在胚胎第16天（E16）注射LPS（80µg/kg; i.p）或生理盐水。将幼崽置于室内空气（RA）或85% O2中14天，随后维持在室内空气中。进行心脏超声心动图、心肌细胞收缩性和分子分析。超声心动图显示，与生理盐水/RA小鼠相比，LPS/O2小鼠在8周时持续左心室下部分式缩短，左心室收缩末期直径更大。与生理盐水/RA对照相比，LPS/O2小鼠分离的心肌细胞收缩和舒张速率较慢，恢复到基线长度的速度较慢。8周时LPS/O2小鼠α-/β-MHC比值升高，Connexin-43水平降低。LPS/O2小鼠的Nox4在第3天至第14天减少，8周时毛细血管密度降低。这些结果表明，母体全身性炎症结合新生儿高氧暴露可诱导心脏结构和功能改变，导致成年期心力衰竭，并支持宫内和新生儿环境对成人健康的重要性。
The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood. Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O2 for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O2 than in saline/RA mice. Isolated cardiomyocytes from LPS/O2 mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O2 mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O2 mice. These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health.
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影响因子：
2.5
作者：
Leviton, Alan;Kuban, Karl C. K.;Paneth, Nigel
通讯作者：
Paneth, Nigel
影响因子：
37.8
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Knuefermann, P;Nemoto, S;Vallejo, JG
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Vallejo, JG
影响因子：
37.8
作者：
Crispi, Fatima;Bijnens, Bart;Gratacos, Eduard
通讯作者：
Gratacos, Eduard
影响因子：
2.5
作者：
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影响因子：
4.2
作者：
Lichtenstein, AH
通讯作者：
Lichtenstein, AH