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.

中文翻译：

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怀孕后，C57BL / 6小鼠的肥胖性心脏肥大加剧。

背景技术在美国，超过三分之一的育龄妇女肥胖，绝经前妇女的心血管疾病（CVD）患病率正在上升。心脏肥大是CVD的独立预测因子。与妊娠相反，在这种情况下，短暂增加的左心室（LV）质量与心脏损害无关，而肥胖介导的心脏肥大是病理性的。缺乏数据说明怀孕期间肥胖对孕妇心血管健康的影响。这项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。方法用雌性C57BL / 6 J小鼠喂养高脂（HF）或低脂（LF）饲料20周。4周后，将LF和HF喂养的雌性小鼠与雄性杂交以使其怀孕或保持未怀孕的对照。分娩后，对幼犬实施安乐死，雌性维持各自的饮食。饮食喂养20周后，通过超声心动图对心脏功能进行定量，并在产后和未产卵的LF和HF喂养的女性中定量测定血浆瘦素和脂联素的浓度。使用NanoString nCounter分析系统从左心室中定量调节心脏肥大和重塑的基因的mRNA丰度。从左心室皮红色的红色染色评估心脏纤维化。结果HF喂养的产后小鼠与HF喂养的未产鼠相比，肥胖引起的体重增加和脂肪膨胀明显增加，与LV量，心输出量和中风量显着增加有关。血浆瘦素而不是脂联素的浓度与HF喂养雌性小鼠的LV质量相关。高频喂养增加了左室后壁的厚度；然而，仅在HF喂养的产后雌性中LV腔直径增加。尽管在HF喂养的产后小鼠中LV质量显着增加，但是在HF喂养的产后小鼠和产后小鼠之间，调节纤维化和间质胶原含量的基因的mRNA丰度相似。相反，仅HF喂养的产后小鼠表现出调节细胞外基质的基因表达改变。结论这些结果表明，妊娠和肥胖的综合作用会增加心脏肥大并促进重塑。绝经前女性中CVD患病率的上升可能归因于BMI超重或肥胖的孕妇进入妊娠期的患病率增加。尽管在HF喂养的产后小鼠中LV质量显着增加，但是在HF喂养的产后小鼠和产后小鼠之间，调节纤维化和间质胶原含量的基因的mRNA丰度相似。相反，仅HF喂养的产后小鼠表现出调节细胞外基质的基因表达改变。结论这些结果表明，妊娠和肥胖的综合作用会增加心脏肥大并促进重塑。绝经前女性中CVD患病率的上升可能归因于BMI超重或肥胖的孕妇进入妊娠期的患病率增加。尽管在HF喂养的产后小鼠中LV质量显着增加，但是在HF喂养的产后小鼠和产后小鼠之间，调节纤维化和间质胶原含量的基因的mRNA丰度相似。相反，仅HF喂养的产后小鼠表现出调节细胞外基质的基因表达改变。结论这些结果表明，妊娠和肥胖的综合作用会增加心脏肥大并促进重塑。绝经前女性中CVD患病率的上升可能归因于BMI超重或肥胖的孕妇进入妊娠期的患病率增加。只有HF喂养的产后小鼠表现出调节细胞外基质的基因表达改变。结论这些结果表明，妊娠和肥胖的综合作用会增加心脏肥大并促进重塑。绝经前女性中CVD患病率的上升可能归因于BMI超重或肥胖的孕妇进入妊娠期的患病率增加。只有HF喂养的产后小鼠表现出调节细胞外基质的基因表达改变。结论这些结果表明，妊娠和肥胖的综合作用会增加心脏肥大并促进重塑。绝经前女性中CVD患病率的上升可能归因于BMI超重或肥胖的孕妇进入妊娠期的患病率增加。