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- Title
MicroRNAs in pulmonary arterial remodeling.
- Authors
Grant, Jennifer S.; White, Kevin; MacLean, Margaret R.; Baker, Andrew H.
- Abstract
Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH.
- Subjects
MICRORNA; PULMONARY artery; HYPERTENSION; HEART diseases; GENETIC mutation; PRECANCEROUS conditions; CELLULAR signal transduction; SURGERY
- Publication
Cellular & Molecular Life Sciences, 2013, Vol 70, Issue 23, p4479
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-013-1382-5