Dataset Information

Expression of the Components of the Renin-Angiotensin System in Venous Malformation.

ABSTRACT: BACKGROUND:Venous malformation (VM) is the most common form of vascular malformation, consisting of a network of thin-walled ectatic venous channels with deficient or absent media. This study investigated the expression of the components of the renin-angiotensin system (RAS), namely, (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (AIITR2) in subcutaneous (SC) and intramuscular (IM) VM. MATERIALS AND METHODS:SC (n?=?7) and IM (n?=?7) VM were analyzed for the expression of PRR, ACE, ATIIR1, and ATIIR2 using 3,3-diaminobenzidine and immunofluorescent (IF) immunohistochemical (IHC) staining and NanoString gene expression analysis. RESULTS:IHC staining showed expression of PRR, ACE, and ATIIR1, and faint expression of ATIIR2 in the endothelium of SC and IM VM. Furthermore, ATIIR2 was expressed by cells away from the endothelium in both SC and IM VM lesions examined. NanoString analysis demonstrated the presence of PRR, ACE, and ATIIR1 but not ATIIR2. CONCLUSION:The presence of PRR, ACE, ATIIR1, and potentially ATIIR2, in both SC and IM VM, suggests a role for the RAS in the biology of VM. This novel finding may lead to a mechanism-based therapy for VM.

SUBMITTER: Siljee S

PROVIDER: S-EPMC4853390 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Expression of the Components of the Renin-Angiotensin System in Venous Malformation.

Siljee Sam S Keane Emily E Marsh Reginald R Brasch Helen D HD Tan Swee T ST Itinteang Tinte T

Frontiers in surgery 20160503

<h4>Background</h4>Venous malformation (VM) is the most common form of vascular malformation, consisting of a network of thin-walled ectatic venous channels with deficient or absent media. This study investigated the expression of the components of the renin-angiotensin system (RAS), namely, (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (AIITR2) in subcutaneous (SC) and intramuscular (IM) VM.<h4>Materials and met ...[more]

PMID: 27200356

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Project description:Improper regulation of signaling in vascular smooth muscle cells (VSMCs) by angiotensin II (AngII) can lead to hypertension, vascular hypertrophy and atherosclerosis. The extent to which the homeostatic levels of the components of signaling networks are regulated through microRNAs (miRNA) modulated by AngII type 1 receptor (AT1R) in VSMCs is not fully understood. Whether AT1R blockers used to treat vascular disorders modulate expression of miRNAs is also not known. To report differential miRNA expression following AT1R activation by AngII, we performed microarray analysis in 23 biological and technical replicates derived from humans, rats and mice. Profiling data revealed a robust regulation of miRNA expression by AngII through AT1R, but not the AngII type 2 receptor (AT2R). The AT1R-specific blockers, losartan and candesartan antagonized >90% of AT1R-regulated miRNAs and AngII-activated AT2R did not modulate their expression. We discovered VSMC-specific modulation of 22 miRNAs by AngII, and validated AT1R-mediated regulation of 17 of those miRNAs by real-time polymerase chain reaction analysis. We selected miR-483-3p as a novel representative candidate for further study because mRNAs of multiple components of the renin-angiotensin system (RAS) were predicted to contain the target sequence for this miRNA. MiR-483-3p inhibited the expression of luciferase reporters bearing 3'-UTRs of four different RAS genes and the inhibition was reversed by antagomir-483-3p. The AT1R-regulated expression levels of angiotensinogen and angiotensin converting enzyme 1 (ACE-1) proteins in VSMCs are modulated specifically by miR-483-3p. Our study demonstrates that the AT1R-regulated miRNA expression fingerprint is conserved in VSMCs of humans and rodents. Furthermore, we identify the AT1R-regulated miR-483-3p as a potential negative regulator of steady-state levels of RAS components in VSMCs. Thus, miRNA-regulation by AngII to affect cellular signaling is a novel aspect of RAS biology, which may lead to discovery of potential candidate prognostic markers and therapeutic targets.

Dataset Information

Expression of the Components of the Renin-Angiotensin System in Venous Malformation.

Publications

Expression of the Components of the Renin-Angiotensin System in Venous Malformation.

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