Reini Seth A, Wood Charles E, Keller-Wood Maureen
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL, USA.
Gene Expr Patterns. 2009 Feb;9(2):122-8. doi: 10.1016/j.gep.2008.09.003. Epub 2008 Sep 21.
The objective of this study was to determine the ontogenetic profiles in left and right ventricle of genes implicated in cardiac growth, including mineralocorticoid (MR) and glucocorticoid (GR) receptor, 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and 2 and genes of the angiotensin system and insulin-like growth factor (IGF) family. Samples from left and right ventricles (LV, RV) were collected from hearts of sheep fetuses at 80, 100, 120, 130, and 145 days of gestation and from newborn lambs. Quantitative real-time PCR was performed to determine the MR, GR, 11beta-HSD 1 and 2, angiotensin converting enzyme (ACE) 1 and 2, IGF1, IGF2, IGF receptors IGF-1R and IGF-2R, and IGF-binding proteins (IGFBP) 2 and 3. In the LV, MR and GR both decreased toward term. In the RV, MR and GR expression did not decrease, but both 11beta-HSD 1 and 2 mRNA levels increased after birth. ACE1 expression in LV and RV sharply increases just before parturition, whereas ACE2 decreased in the LV and RV in late gestation. IGF2, IGF2R, and IGFBP2 expression levels substantially decreased in late gestation in LV and RV; IGF2R also decreased with age in LV. These patterns suggest that reduced expression of genes related to IGF and angiotensin II action occur as proliferative activity declines and terminal differentiation occurs in the late gestation fetal heart.
本研究的目的是确定与心脏生长相关基因在左心室和右心室中的个体发育情况,这些基因包括盐皮质激素(MR)和糖皮质激素(GR)受体、11β-羟基类固醇脱氢酶(11β-HSD)1和2、血管紧张素系统基因以及胰岛素样生长因子(IGF)家族基因。从妊娠80、100、120、130和145天的绵羊胎儿心脏以及新生羔羊心脏中采集左心室和右心室(LV,RV)样本。采用定量实时PCR检测MR、GR、11β-HSD 1和2、血管紧张素转换酶(ACE)1和2、IGF1、IGF2、IGF受体IGF-1R和IGF-2R以及IGF结合蛋白(IGFBP)2和3。在左心室中,MR和GR均在足月时下降。在右心室中,MR和GR表达未下降,但出生后11β-HSD 1和2的mRNA水平均升高。左心室和右心室中的ACE1表达在分娩前急剧增加,而ACE2在妊娠晚期左心室和右心室中均下降。IGF2、IGF2R和IGFBP2的表达水平在妊娠晚期左心室和右心室中大幅下降;左心室中的IGF2R也随年龄增长而下降。这些模式表明,随着妊娠晚期胎儿心脏增殖活性下降和终末分化的发生,与IGF和血管紧张素II作用相关基因的表达降低。