Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice
Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice
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DOI：
10.1186/s13293-019-0269-z
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发表时间：
2019-12-16
影响因子：
7.9
通讯作者：
Shoemaker, Robin
中科院分区：
文献类型：
--
作者：
Che, Chen;Dudick, Kayla;Shoemaker, Robin
背景：在美国，超过三分之一的育龄妇女肥胖，绝经前妇女心血管疾病（CVD）的患病率正在上升。心脏肥厚是CVD的独立预测因子。与妊娠期相比，短暂的左心室（LV）重量增加与心脏损伤无关，肥胖介导的心脏肥厚是病理性的。描述怀孕期间肥胖对产妇心血管健康影响的数据缺乏。本研究的目的是确定怀孕期间肥胖对小鼠心脏功能和结构的长期影响。方法雌性C57BL/6 J小鼠分别饲喂高脂（HF）和低脂（LF）饲料20周。4周后，喂食LF和hf的雌性小鼠与雄性小鼠杂交，使其怀孕或保持未怀孕的对照组。分娩后，幼崽被安乐死，雌性维持各自的饮食。饲粮喂养20周后，通过超声心动图定量心功能，并定量LF和hf喂养的产后和未产雌性血浆瘦素和脂联素浓度。利用NanoString nCounter分析系统定量分析左心室心肌肥厚和重构调控基因的mRNA丰度。左心室微天狼星红染色评价心肌纤维化。结果：与未分娩小鼠相比，高频喂养的产后小鼠体重明显增加，脂肪量增加，左室质量、心输出量和卒中量显著增加。在hf喂养的雌性中，血浆瘦素浓度与左室质量相关，而非脂联素浓度。HF喂养增加左室后壁厚度；然而，只有喂食hf的产后雌性左室直径增加。尽管产后小鼠的左室质量明显增加，但在未分娩小鼠和产后小鼠中，调节纤维化和间质胶原含量的基因mRNA丰度相似。相比之下，只有喂食hf的产后小鼠表现出调节细胞外基质基因的表达改变。结论妊娠与肥胖的联合作用增加了心肌肥厚，促进了心肌重构。绝经前妇女心血管疾病患病率的上升可能归因于体重指数超重或肥胖的怀孕妇女患病率的增加。
Background Over a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice. Methods Female C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles. Results HF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix. Conclusions These results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.