Vascular smooth muscle cell phenotypic transition regulates gap junctions of cardiomyocyte

Heart Vessels. 2020 Jul;35(7):1025-1035. doi: 10.1007/s00380-020-01602-3. Epub 2020 Apr 8.

Abstract

Atrial fibrillation (AF) is one of the most prevalent arrhythmias. Myocardial sleeves of the pulmonary vein are critical in the occurrence of AF. Our study aims to investigate the effect of synthetic vascular smooth muscle cells (SMCs) on gap junction proteins in cardiomyocytes. (1) Extraction of vascular SMCs from the pulmonary veins of Norway rats. TGF-β1 was used to induce the vascular SMCs switching to the synthetic phenotype and 18-α-GA was used to inhibit gap junctions of SMCs. The contractile and synthetic phenotype vascular SMCs were cocultured with HL-1 cells; (2) Western blotting was used to detect the expression of Cx43, Cx40 and Cx45 in HL-1 cells, and RT-PCR to test microRNA 27b in vascular SMCs or in HL-1 cells; (3) Lucifer yellow dye transfer experiment was used to detect the function of gap junctions. (1) TGF- β1 induced the vascular SMCs switching to synthetic phenotype; (2) Cx43 was significantly increased, and Cx40 and Cx45 were decreased in HL-1 cocultured with synthetic SMCs; (3) The fluorescence intensity of Lucifer yellow was higher in HL-1 cocultured with synthetic SMCs than that in the cells cocultured with contractile SMCs, which was inhibited by18-α-GA; (4) the expression of microRNA 27b was increased in HL-1 cocultured with synthetic SMCs, which was attenuated markedly by 18-α-GA. (5) the expression of ZFHX3 was decreased in HL-1 cocultured with synthetic SMCs, which was reversed by 18-α-GA. The gap junction proteins of HL-1 were regulated by pulmonary venous SMCs undergoing phenotypic transition in this study, accompanied with the up-regulation of microRNA 27b and the down-regulation of ZFHX3 in HL-1 cells, which was associated with heterocellular gap junctions between HL-1 and pulmonary venous SMCs.

Keywords: Cardiomyocyte; Connexin; MicroRNA 27b; Phenotypic transition; Smooth muscle cell.

MeSH terms

  • Animals
  • Cell Communication* / drug effects
  • Cell Line
  • Cell Plasticity* / drug effects
  • Coculture Techniques
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Connexins / genetics
  • Connexins / metabolism*
  • Gap Junction alpha-5 Protein
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism*
  • Glycyrrhetinic Acid / analogs & derivatives
  • Glycyrrhetinic Acid / pharmacology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Phenotype
  • Pulmonary Veins / metabolism
  • Rats
  • Signal Transduction
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Connexin 43
  • Connexins
  • Gja1 protein, rat
  • Homeodomain Proteins
  • MIRN27 microRNA, rat
  • MicroRNAs
  • Transforming Growth Factor beta1
  • Zfhx3 protein, rat
  • connexin 45
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid