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Published on: November 30, 2013
Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression
Clemens L Bockmeyer1, Lavinia Maegel, Sabina Janciauskiene
1Institute of Pathology, Hannover Medical School, Hannover, Germany. bockmeyer.clemens@mh-hannover.de
Background:
Recent studies have revealed that microRNAs (miRNAs) play a key role in the control of angiogenesis and vascular remodeling. Specific miRNAs in plexiform vasculopathy of severe pulmonary arterial hypertension (PAH) in humans have not yet been investigated.
Methods:
We analyzed expression of miR-143/145 (vascular smooth muscle-specific), miR-126 (endothelial-specific) and related mRNAs in plexiform (PLs) and concentric lesions (CLs), which had been laser-microdissected from specimens of formalin-fixed, paraffin-embedded, explanted lungs of PAH patients (n = 12) and unaffected controls (n = 8). Samples were analyzed by real-time polymerase chain reaction, and protein expression was determined by immunohistochemistry.
Results:
Expression levels of miR-143/145 and its target proteins (e.g., myocardin, smooth muscle myosin heavy chain) were found to be significantly higher in CLs than in PLs, whereas miR-126 and VEGF-A were significantly up-regulated in PLs when compared with CLs, indicating a more prominent angiogenic phenotype of PL. This correlates with a down-regulation of miR-204 as well as an up-regulation of miR-21 in PLs, which in turn corresponds to enhanced cell proliferation.
Conclusions:
Our findings show that morphologic changes of plexiform vasculopathy in the end-stage PAH lung are reflected by alterations at the miRNA level.
Insights
MicroRNAs (miRNAs) show altered expression in pulmonary arterial hypertension (PAH) lung lesions. Specific miRNA changes reflect the distinct morphologic features of plexiform vasculopathy in PAH.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pulmonary Hypertension Research
Background:
- MicroRNAs (miRNAs) are critical regulators of angiogenesis and vascular remodeling.
- The specific role of miRNAs in plexiform vasculopathy within severe pulmonary arterial hypertension (PAH) remains unexplored.
Purpose of the Study:
- To investigate the expression profiles of specific miRNAs (miR-143/145, miR-126) and related targets in distinct vascular lesions of PAH.
- To correlate miRNA expression with cellular phenotypes in plexiform and concentric lesions.
Main Methods:
- Laser-microdissection of plexiform lesions (PLs) and concentric lesions (CLs) from explanted PAH lungs and controls.
- Analysis of miRNA and mRNA expression using real-time polymerase chain reaction.
- Assessment of protein expression via immunohistochemistry.
Main Results:
- Vascular smooth muscle-specific miR-143/145 and targets were elevated in CLs compared to PLs.
- Endothelial-specific miR-126 and VEGF-A were upregulated in PLs, suggesting a more angiogenic phenotype.
- miR-204 was downregulated and miR-21 upregulated in PLs, correlating with increased cell proliferation.
Conclusions:
- Morphological alterations in plexiform vasculopathy of end-stage PAH lungs are mirrored by distinct changes in miRNA expression.
- These findings highlight the involvement of specific miRNAs in the pathogenesis of PAH vascular remodeling.
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