Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: implications for the pathogenesis of thoracoabdominal aorta aneurysm

Pharmazie. 2015 May;70(5):310-5.

Abstract

Long non-coding RNAs (IncRNAs) play important roles in various biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about the role of IncRNA HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) in regulating the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) and the expression of HIF1a-AS1 in serum of thoracoabdominal aortic aneurysm (TAAA) patients. The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting, respectively. Cells were transfected with siRNAs as a gene silencing method. In serum of TAAA patients, the expression of HIF1a-AS1 was significantly increased (superior to 6-fold) compared to the normal control. Moreover, Palmitic acid (PA) induced cell apoptosis in VSMCs in a time- and dose-dependent manner, and the proportion of the apoptotic cells had gained as compared to untreatment group. PA also induced up-regulation expression of HIF1a-AS1. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase-3 and caspase-8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. HIF1a-AS1 was overexpressed in the TAAA and the interaction between HIF1a-AS1 and apoptotic proteins plays a key role in the proliferation and apoptosis of VSMCs in vitro, which may contribute to the pathogenesis of TAAA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta, Abdominal
  • Aorta, Thoracic
  • Aortic Aneurysm, Thoracic / pathology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / biosynthesis
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Muscle, Smooth, Vascular / drug effects*
  • RNA Interference
  • RNA, Antisense / pharmacology*
  • RNA, Long Noncoding / pharmacology*

Substances

  • Apoptosis Regulatory Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Antisense
  • RNA, Long Noncoding