Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression

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• 作者：Clemens L. Bockmeyer ; MD^a ; ^{bockmeyer.clemens@mh-hannover.de} ; Lavinia Maegel^a ; ^b ; Sabina Janciauskiene ; MD^c ; Johanna Rische^a ; Ulrich Lehmann ; PhD^a ; Ulrich A. Maus ; MD^b ; Nils Nickel ; MD^c ; Axel Haverich ; MD^d ; Marius M. Hoeper ; MD^c ; Heiko A. Golpon ; MD^c ; Hans Kreipe ; MD^a ; Florian Laenger ; MD^a ; ^e ; Danny Jonigk ; MD^a ; ^e
• 关键词：microRNA ; laser microdissection ; vascular remodeling ; pulmonary arterial hypertension
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：31
• 期：7
• 页码：764-772
• 全文大小：2515 K

文摘

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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.