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Emerging role of epigenetic in pulmonary arterial hypertension right ventricular failure
Author(s) -
Potus Francois,
Ruffenach Gregoire,
Provencher Steeve,
Bonnet Sébastien
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.630.7
Subject(s) - angiogenesis , epigenetics , microrna , long non coding rna , cancer research , downregulation and upregulation , pulmonary hypertension , medicine , biology , endocrinology , gene , genetics
Pulmonary arterial hypertension (PAH) is associated with a global impairment of angiogenesis. Although the origin of the angiogenic defect remains unknown. since a few years epigenetic has become an important research area in many diseases including PAH. Role for miRNAs has been widely demonstrated; nonetheless a role for long noncoding RNA (LncRNA) remains unknown. In the present study we focused our role on the expression level of miR‐126 and MALAT‐1 both of which are enriched in endothelial cells and known to be implicated in angiogenesis regulation. We hypothesized that aberrantly express miR‐126 and MALAT‐1 contributes to angiogenesis impairment see in PAH . RESULTS Using qRT‐PCR we showed that miR126 was decreased in human PAH RV (p<0.05) compare to control while MALAT‐1 expression was upregulated p<0.05). These finding were associated in vitro with a significant reduction in EC proliferation (Ki67;p<0.05) and tube formation (p<0.05) measured in freshly isolated human RV endothelial cells from both PAH compare to EC from control RV. Both miR‐126 and MALAT‐1 are critical regulators of angiogenesis and are likely dependent of each other; in fact we showed that miR‐126 expression inversely correlates with MALAT‐1 expression in PAH RV (p<0.05).CONCLUSION We demonstrated, for the first time in PAH that the endothelial‐enriched noncoding RNAs miR‐126 and MALAT‐1 are aberrantly expressed in human RV from PAH patients contributing to the impairment of angiogenesis. The endothelial specific miR‐126 is known to regulate endothelial cells proliferation while MALAT‐1 up regulation has been associated with decreased endothelial cells migration and sprouting, suggesting that these two noncoding RNAs are implicated in angiogenesis defect.