Vascular smooth muscle cell phenotypic transition regulates gap junctions of cardiomyocyte

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-β 1 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-β 1 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.

Analyses of m6A regulatory genes and subtype classification in atrial fibrillation

“…Most AF-causing foci are located near the pulmonary veins’ ostium, where myocardial cells and vascular smooth muscle cells interlace ( Wijffels et al, 1995 ; Haissaguerre et al, 1998 ; Carballo et al, 2018 ). Gap junction proteins in cardiomyocytes are regulated by the phenotypic transition of pulmonary vein vascular smooth muscle cells, leading to heterolytic junctions and AF occurrence ( Zhou et al, 2020 ). KEGG analysis revealed that the vascular smooth muscle contraction pathway was significantly enriched, suggesting that the m6A gene may be involved in regulating vascular smooth muscle cells on cardiomyocytes, leading to AF.…”

Myofibroblast specific targeting approaches to improve fibrosis treatment

“…Myofibroblasts are connected by gap junctions and have similar features to smooth muscle cells. 12 Commonly expressed in mesenchymal cells, myofibroblasts express fibroblast surface protein (FSP) and vimentin. 13 Since FMT is regulated by processes that are essential for normal body functions, using targeted treatment approaches is essential.…”

“…Myofibroblasts are connected by gap junctions and have similar features to smooth muscle cells. 12 Commonly expressed in mesenchymal cells, myofibroblasts express fibroblast surface protein (FSP) and vimentin. 13…”

Cardiac Tissue Engineering: Inclusion of Non-cardiomyocytes for Enhanced Features

“…Smooth muscle cells (SMCs) play an important role in the heart; they regulate the tone of blood vessels ( Brozovich et al, 2016 ), and at the molecular level, SMCs affect gap junctions and the expression of Cx43 in CM ( Zhou et al, 2020 ). Transplantation of SMC, EC, and CM co-cultures improves heart function after myocardial infarction (MI) in animal models ( Ye et al, 2015 ; Gao et al, 2018 ).…”