Folguieri Marina S, Franco Ana Teresa Barufi, Vieira André Schwambach, Gontijo José Antonio Rocha, Boer Patricia Aline
Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, FCM, Campinas, Brazil.
Department of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, Brazil.
Front Cell Dev Biol. 2022 Oct 24;10:892322. doi: 10.3389/fcell.2022.892322. eCollection 2022.
Adverse factors that influence embryo/fetal development are correlated with increased risk of cardiovascular disease (CVD), type-2 diabetes, arterial hypertension, obesity, insulin resistance, impaired kidney development, psychiatric disorders, and enhanced susceptibility to oxidative stress and inflammatory processes in adulthood. Human and experimental studies have demonstrated a reciprocal relationship between birthweight and cardiovascular diseases, implying intrauterine adverse events in the onset of these abnormalities. In this way, it is plausible that confirmed functional and morphological heart changes caused by gestational protein restriction could be related to epigenetic effects anticipating cardiovascular disorders and reducing the survival time of these animals. Wistar rats were divided into two groups according to the protein diet content offered during the pregnancy: a normal protein diet (NP, 17%) or a Low-protein diet (LP, 6%). The arterial pressure was measured, and the cardiac mass, cardiomyocytes area, gene expression, collagen content, and immunostaining of proteins were performed in the cardiac tissue of male 62-weeks old NP compared to LP offspring. In the current study, we showed a low birthweight followed by catch-up growth phenomena associated with high blood pressure development, increased heart collagen content, and cardiomyocyte area in 62-week-old LP offspring. mRNA sequencing analysis identified changes in the expression level of 137 genes, considering genes with a -value < 0.05. No gene was. Significantly changed according to the adj-p-value. After gene-to-gene biological evaluation and relevance, the study demonstrated significant differences in genes linked to inflammatory activity, oxidative stress, apoptosis process, autophagy, hypertrophy, and fibrosis pathways resulting in heart function disorders. The present study suggests that gestational protein restriction leads to early cardiac diseases in the LP progeny. It is hypothesized that heart dysfunction is associated with fibrosis, myocyte hypertrophy, and multiple abnormal gene expression. Considering the above findings, it may suppose a close link between maternal protein restriction, specific gene expression, and progressive heart failure.
影响胚胎/胎儿发育的不利因素与心血管疾病（CVD）、2型糖尿病、动脉高血压、肥胖、胰岛素抵抗、肾脏发育受损、精神障碍以及成年后对氧化应激和炎症过程易感性增加的风险相关。人类和实验研究表明出生体重与心血管疾病之间存在相互关系，这意味着这些异常的发生存在宫内不良事件。通过这种方式，妊娠蛋白质限制引起的已证实的心脏功能和形态变化可能与预测心血管疾病并缩短这些动物存活时间的表观遗传效应有关。将Wistar大鼠根据孕期提供的蛋白质饮食含量分为两组：正常蛋白质饮食（NP，17%）或低蛋白饮食（LP，6%）。测量动脉血压，并对62周龄雄性NP后代与LP后代的心脏组织进行心脏质量、心肌细胞面积、基因表达、胶原蛋白含量和蛋白质免疫染色检测。在本研究中，我们发现62周龄LP后代出生体重低，随后出现追赶生长现象，伴有高血压发展、心脏胶原蛋白含量增加和心肌细胞面积增大。mRNA测序分析确定了137个基因表达水平的变化，考虑的基因p值<0.05。根据校正p值，没有基因有显著变化。经过基因间生物学评估和相关性分析，研究表明与炎症活动、氧化应激、凋亡过程、自噬、肥大和纤维化途径相关的基因存在显著差异，导致心脏功能障碍。本研究表明妊娠蛋白质限制会导致LP后代早期出现心脏疾病。据推测，心脏功能障碍与纤维化、心肌细胞肥大和多个异常基因表达有关。考虑到上述发现，可能认为母体蛋白质限制、特定基因表达和进行性心力衰竭之间存在密切联系。
