Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress

Zhang, Zongqi; Chen, Yizhu; Zhang, Tiantian; Guo, Lei; Yang, Wenlong; Zhang, Junfeng; Wang, Changqian

doi:10.1159/000445636

Cited by 22 publications

(29 citation statements)

References 50 publications

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“…209,210 A change in connexin expression in myoendothelial gap junctions was also found to be involved in endothelial control of smooth muscle phenotype switch in response to shear stress. 211…”

Section: F I G U R Ementioning

confidence: 99%

Connexins in the control of vasomotor function

Pogoda

Kameritsch

Mannell³

et al. 2018

Acta Physiologica

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Vascular endothelial cells, as well as smooth muscle cells, show heterogeneity with regard to their receptor expression and reactivity. For the vascular wall to act as a functional unit, the various cells' responses require integration. Such an integration is not only required for a homogeneous response of the vascular wall, but also for the vasomotor behaviour of consecutive segments of the microvascular arteriolar tree. As flow resistances of individual sections are connected in series, sections require synchronization and coordination to allow effective changes of conductivity and blood flow. A prerequisite for the local coordination of individual vascular cells and different sections of an arteriolar tree is intercellular communication. Connexins are involved in a dual manner in this coordination. (i) By forming gap junctions between cells, they allow an intercellular exchange of signalling molecules and electrical currents. In particular, the spread of electrical currents allows for coordination of cell responses over longer distances. (ii) Connexins are able to interact with other proteins to form signalling complexes. In this way, they can modulate and integrate individual cells' responses also in a channel-independent manner. This review outlines mechanisms allowing the vascular connexins to exert their coordinating function and to regulate the vasomotor reactions of blood vessels both locally, and in vascular networks. Wherever possible, we focus on the vasomotor behaviour of small vessels and arterioles which are the main vessels determining vascular resistance, blood pressure and local blood flow.

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Section: F I G U R Ementioning

confidence: 99%

Connexins in the control of vasomotor function

Pogoda

Kameritsch

Mannell³

et al. 2018

Acta Physiologica

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“…In hypertensive patients, the circulating transforming growth factor-β 1 (TGF-β 1 ) is significantly increased [25], a pivotal factor to induce the phenotypic transition of contractile-like SMCs to synthetic-like cells [26]. In this study, we used TGF-β 1 to induce SMCs with synthetic phenotype as evidenced by the notable diffusing actin, increased collagen I and vimentin, and decreased calponin as described in our previous study [27].…”

Section: Discussionmentioning

confidence: 92%

Vascular smooth muscle cell phenotypic transition regulates gap junctions of cardiomyocyte

Zhou

Zhang

et al. 2020

Heart Vessels

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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.

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“…This model mimicked well the MEGJs in the intact vasculature, which is located in the internal elastic lamina, and is constructed by the projections of VECs and VSMCs. Although this model has been widely used to study the function and mechanism of MEGJs in different disease models (5,7,9,(42)(43)(44), as a simplified coculture model it has limitations compared with the real in vivo physiological system. As we know, the regulation of Cx relies on the combined effects of the complicated hormone and mechanical environments.…”

Section: Discussionmentioning

confidence: 99%

“…For example, MEGJ-mediated communication contributed to smooth muscle cell hyperpolarization and dilation induced by endothelium-dependent hyperpolarizing factor (EDHF) in the middle cerebral artery of rats (30). Additionally, the gap junction inhibitory peptides 40 Gap27, 37,43 Gap27, and 43 Gap26 decreased endothelium-dependent contractions in the aortas of spontaneously hypertensive rats (32). These findings suggest that MEGJmediated communication helps regulate signal transfer from VECs to VSMCs and subsequently VSMCs contractile function.…”

mentioning

confidence: 91%

Myoendothelial gap junctions mediate regulation of angiopoietin-2-induced vascular hyporeactivity after hypoxia through connexin 43-gated cAMP transfer

Yang

et al. 2017

American Journal of Physiology-Cell Physiology

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Angiopoietin-2 (Ang-2) contributes to vascular hyporeactivity after hemorrhagic shock and hypoxia through upregulation of inducible nitric oxide synthase (iNOS) in a vascular endothelial cell (VEC)-specific and Ang-2/Tie2 receptor-dependent manner. While iNOS is primarily expressed in vascular smooth muscle cells (VSMCs), the mechanisms of signal transfer from VECs to VSMCs are unknown. A double-sided coculture model with VECs and VSMCs from Sprague-Dawley rats was used to investigate the role of myoendothelial gap junctions (MEGJs), the connexin (Cx) isoforms involved, and other relevant mechanisms. After hypoxia, VSMCs treated with exogenous Ang-2 showed increased iNOS expression and hyporeactivity, as well as MEGJ formation and communication. These Ang-2 effects were suppressed by the MEGJ inhibitor 18α-glycyrrhetic acid (18-GA), siRNA, or siRNA. Reagents antagonizing cAMP or protein kinase A (PKA) in VECs inhibited Cx43 expression in MEGJs, decreasing MEGJ formation and associated communication, after hypoxia following Ang-2 treatment. The increased cAMP levels in VSMCs and transfer of Alexa Fluor 488-labeled cAMP from VECs to VSMCs, after hypoxia following Ang-2 treatment, was antagonized by siRNA. A cAMP antagonist added to VECs or VSMCs inhibited both increased iNOS expression and hyporeactivity in VSMCs subjected to hypoxia following Ang-2 treatment. Based on these findings, we propose that Cx43 was the Cx isoform involved in MEGJ-mediated VEC-dependent regulation of Ang-2, which induces iNOS protein expression and vascular hyporeactivity after hypoxia. Cx43 was upregulated by cAMP and PKA, permitting cAMP transfer between cells.

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Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress

Cited by 22 publications

References 50 publications

Connexins in the control of vasomotor function

Connexins in the control of vasomotor function

Vascular smooth muscle cell phenotypic transition regulates gap junctions of cardiomyocyte

Myoendothelial gap junctions mediate regulation of angiopoietin-2-induced vascular hyporeactivity after hypoxia through connexin 43-gated cAMP transfer

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