Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation

Hsieh, Yi‐Ting; Liu, Norika Mengchia; Ohmori, Eriko; Yokota, Tomohiro; Kajimura, Ichige; Akaike, Toru; Ohshima, Toshio; Goda, Nobuhito; Minamisawa, Susumu

doi:10.1253/circj.cj-13-1029

Cited by 22 publications

(14 citation statements)

References 21 publications

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“…Several transcriptomic studies have been reported previously in mice and rats; however, these have had different experimental designs or utilized single developmental time points for comparison, thereby limiting their ability to identify genes whose developmental changes are unique to the DA (2–6). A study in the rat examined changes in gene expression between DA and aorta at day 19 and 21 (3). We reanalyzed the microarray data from this study and compared it with the present study.…”

Section: Discussionmentioning

confidence: 99%

Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition

Goyal

Longo

et al. 2016

Pediatr Res

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BACKGROUND Patent ductus arteriosus (PDA) in the newborn is the most common congenital heart anomaly and is significantly more common in preterm infants. Contemporary pharmacological treatment is effective in only 70–80% of the cases. Moreover, indomethacin or ibuprofen, which are used to close a PDA may be accompanied by serious side effects in premature infants. To explore the novel molecular pathways, which may be involved in the maturation and closure of the ductus arteriosus (DA), we used fetal and neonatal sheep to test the hypothesis that maturational development of DA is associated with significant alterations in specific mRNA expression. METHODS We conducted oligonucleotide microarray experiments on the isolated mRNA from DA and ascending aorta from three study groups (premature fetus—97 ± 0 d, near-term fetus—136 ± 0.8 d, and newborn lamb—12 ± 0 h). We compared the alterations in mRNA expression in DA and aorta to identify genes specifically involved in DA maturation. RESULTS Results demonstrate significant changes in wingless–integrin1, thrombospondin 1, receptor activator of nuclear factor-kappa B, nitric oxide synthase, and retinoic acid receptor activation signaling pathways. CONCLUSION We conclude that these pathways may play an important role during both development and postnatal DA closure and warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition

Goyal

Longo

et al. 2016

Pediatr Res

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“…After centrifugation at 12,000 g at 4˚C for 15 minutes, the supernatant was collected. Microarray analysis was performed as previously described [5,6]. Briefly, total mRNA was extracted following the instructions attached to the kit.…”

Section: Microarray Analysismentioning

confidence: 99%

Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1

et al. 2020

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Myocardial fibrosis is often associated with cardiac hypertrophy; indeed, fibrosis is one of the most critical factors affecting prognosis. We aimed to identify the molecules involved in promoting fibrosis under hypertrophic stimuli. We previously established a rat model of cardiac hypertrophy by pulmonary artery banding, in which approximately half of the animals developed fibrosis in the right ventricle. Here, we first comprehensively analyzed mRNA expression in the right ventricle with or without fibrosis in pulmonary artery banding model rats by DNA microarray analysis (GSE141650 at NCBI GEO). The expression levels of 19 genes were up-regulated more than 1.5-fold in fibrotic hearts compared with non-fibrotic hearts. Among them, fibrosis growth factor (FGF) 23 showed one of the biggest increases in expression. Real-time PCR analysis also revealed that, among the FGF receptor (FGFR) family, FGFR1 was highly expressed in fibrotic hearts. We then found that FGF23 was expressed predominantly in cardiomyocytes, while FGFR1 was predominantly expressed in fibroblasts in the rat ventricle. Next, we added FGF23 and transforming growth factor (TGF)-β1 (10-50 ng/mL of each) to isolated fibroblasts from normal adult rat ventricles and cultured them for three days. While FGF23 itself did not directly affect the expression levels of any fibrosis-related mRNAs, FGF23 enhanced the effect of TGF-β1 on increasing the expression levels of α-smooth muscle actin (α-SMA) mRNA. This increase in xx-SMA mRNA levels due to the combination of TGF-β1 and FGF23 was attenuated by the inhibition of FGFR1 or the knockdown of FGFR1 in fibroblasts. Thus, FGF23 synergistically promoted the activation of fibroblasts with TGF-β1, transforming fibroblasts into myofibroblasts via FGFR1. Thus, we identified FGF23 as a paracrine factor secreted from cardiomyocytes to promote cardiac fibrosis under conditions in which TGF-β1 is activated. FGF23 could be a possible target to prevent fibrosis following myocardial hypertrophy.

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“…Tropoelastin is a chemoattractant for SMCs. Lysl oxidase (LOX) catalyzes elastin cross-linking and it is degraded in the ductal cell when EP 4 receptor is stimulated by the prostaglandins ( 77 ). EP 4 is a Gs protein coupled receptor which increases intracellular cAMP by adenylyl cyclases.…”

Section: Anatomic Closure and Remodelingmentioning

confidence: 99%

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

Ovalı

2020

Front. Pediatr.

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Failure of ductus arteriosus closure after preterm birth is associated with significant morbidities. Ductal closure requires and is regulated by a complex interplay of molecular and mechanical mechanisms with underlying genetic factors. In utero patency of the ductus is maintained by low oxygen tension, high levels of prostaglandins, nitric oxide and carbon monoxide. After birth, ductal closure occurs first by functional closure, followed by anatomical remodeling. High oxygen tension and decreased prostaglandin levels mediated by numerous factors including potassium channels, endothelin-1, isoprostanes lead to the contraction of the ductus. Bradykinin and corticosteroids also induce ductal constriction by attenuating the sensitivity of the ductus to PGE2. Smooth muscle cells of the ductus can sense oxygen through a mitochondrial network by the role of Rho-kinase pathway which ends up with increased intracellular calcium levels and contraction of myosin light chains. Anatomical closure of the ductus is also complex with various mechanisms such as migration and proliferation of smooth muscle cells, extracellular matrix production, endothelial cell proliferation which mediate cushion formation with the interaction of blood cells. Regulation of vessel walls is affected by retinoic acid, TGF-β1, notch signaling, hyaluronan, fibronectin, chondroitin sulfate, elastin, and vascular endothelial cell growth factor (VEGF). Formation of the platelet plug facilitates luminal remodeling by the obstruction of the constricted ductal lumen. Vasa vasorum are more pronounced in the term ductus but are less active in the preterm ductus. More than 100 genes are effective in the prostaglandin pathway or in vascular smooth muscle development and structure may affect the patency of ductus. Hemodynamic changes after birth including fluid load and flow characteristics as well as shear forces within the ductus also stimulate closure. Current pharmacological treatment for the closure of a patent ductus is based on the blockage of the prostaglandin pathway mainly through COX or POX inhibition, albeit with some limitations and side effects. Further research for new agents aiming ductal closure should focus on a clear understanding of vascular biology of the ductus.

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Transcription Profiles of the Ductus Arteriosus in Brown-Norway Rats With Irregular Elastic Fiber Formation

Cited by 22 publications

References 21 publications

Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition

Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition

Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

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