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Introduction

Pulmonary Arterial Hypertension (PAH) is a progressively devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. The proliferation of cancer cells is mediated by increased expression of Enhancer of Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes. However, the role of EZH2 in PAH has not been studied. In this study, it is hypothesized that EZH2 could play a role in the proliferation of PASMCs.

Methods

In the present study, the expression patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The effects of EZH2 overexpression on the proliferation of human PASMCs were tested. PASMCs were transfected with EZH2 or GFP using nucleofector system. After transfection, the cells were incubated for 48 hours at 37°C. Proliferation and cell cycle analysis were performed using flow cytometry. Apoptosis of PASMCs was determined using annexin V staining and cell migration was tested by wound healing assay.

Results

EZH2 protein expression in mouse PASMCs were correlated with an increase in right ventricular systolic pressure and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected cells, there was a 3.5 fold increase in proliferation, while there was a significant decrease in the rate of apoptosis of PASMCs, when compared to control.

Conclusion

These findings suggest that EZH2 plays a role in the migration and proliferation of PASMCs, which is a major hallmark in PAH. It also suggests that EZH2 could play a role in the development of PAH and can serve as a potential target for new therapies for PAH."xsd:string
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http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Bao H."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Mohapatra S.S."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Rajanbabu V."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Kolliputi N."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Lockey R."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Aljubran S.A."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Cox R. Jr."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Kollongod Ramanathan G."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Mohapatra S.M."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/author"Tamarapu Parthasarathy P."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/pages"e37712"xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/title"Enhancer of zeste homolog 2 induces pulmonary artery smooth muscle cell proliferation."xsd:string
http://purl.uniprot.org/citations/22662197http://purl.uniprot.org/core/volume"7"xsd:string
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