Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells.
Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure.
Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands ; Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands.
Regina
R
Bökenkamp
Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands ; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium.
Ronald
R
van Brempt
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Jacoba Cornelia
JC
van Munsteren
Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium.
Ilse
I
van den Wijngaert
Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium.
Ronald
R
de Hoogt
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Livio
L
Finos
Biostatistics, Department for Health Evidence, Radboud University Medical Center, Nimegen, The Netherlands.
Jelle
J
Goeman
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands ; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Adriana Cornelia Gittenberger-de
AC
Groot
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Robert Eugen
RE
Poelmann
Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Nicolaas Andreas
NA
Blom
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Marcus Cornelis
MC
DeRuiter
D000818:Animals; D004373:Ductus Arteriosus / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D061346:Laser Capture Microdissection; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D020710:RGS Proteins; C491348:Rgs5 protein, rat; D014157:Transcription Factors