Cyclic Nucleotides Differentially Regulate Cx43 Gap Junction Function in Uterine Artery Endothelial Cells From Pregnant Ewes

Ampey, Bryan C.; Ampey, Amanda C.; López, Gladys; Bird, Ian M.; Magness, Ronald R.

doi:10.1161/hypertensionaha.117.09113

Cited by 15 publications

(9 citation statements)

References 31 publications

(100 reference statements)

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“…7). 10,[20][21][22] In the present study, LRP6 interference fragments could aggravate hypoxia injury of Cx43. The overexpression of LRP6 could signi cantly increase the protein level and phosphorylation level of Cx43, but the interference with LRP6 showed the opposite trend.…”

Section: Discussionsupporting

confidence: 47%

LRP6 modulates the phosphorylation of Cx43 via Gαs in ventricular tachycardia of myocardial infarction

Zhang

Liu²,

Cai

et al. 2022

Preprint

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Background Ventricular tachycardia (VT) and ventricular fibrillation are the most causes of early death in patients with myocardial infarction (MI). This study was aimed to explore whether LRP6 and its upstream genes circRNA1615 and miR-152-3p modulated the phosphorylation of Connexin-43 (Cx43) via Gαs in ventricular tachycardia of MI.Method we constructed the hypoxia cardiomyocyte model and AMI mice, and explored the modulation relationship of LRP6 and its upstream genes circRNA1615 and miR-152-3p. In addition, the immunoblot analysis with monoclonal and polyclonal antibodies were used to detect whether LRP6 and Cx43 were phosphorylated, further investigated that the LRP6 regulated the phosphorylation of its downstream target Cx43 via G-protein alpha subunit Gαs by using cell transfection, FISH assay, HE staining, RT-qPCR, and Western blot techniques.Result LRP6 mRNA expression was significantly reduced in AMI group compared with the control group. Hypoxia could inhibit the protein and phosphorylation levels of LRP6 and Cx43. The expression of circRNA1615 in AMI mice was significantly decreased, but overexpression of circRNA1615 significantly reversed the inhibitory effect of AMI. Also overexpression of circRNA1615 could weaken the effect of miR-152-3p mimic, and the miR-152-3p mimic increased the hypoxia injury of LRP6 and Cx43, further LRP6 interference fragments could aggravate hypoxia injury of Cx43. The overexpression of LRP6 could significantly increase the protein level and phosphorylation level of Cx43, but the interference with LRP6 showed the opposite trend. Noticeably, the interference with Gαs weakened the protein and phosphorylation levels of Cx43, however, the interference with LRP6 further inhibited the protein and phosphorylation levels of Cx43. Finally, the transcriptions of circRNA1615 and LRP6 were inhibited in AMI, but the transcription of miR-152-3p was promoted, and the overexpression of circRNA1615 could weaken the damage effect and VT of AMI.Conclusion LRP6 and its upstream genes circRNA1615 and miR-152-3p modulated the phosphorylation of Cx43 via Gαs in ventricular tachycardia of myocardial infarction.

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Section: Discussionsupporting

confidence: 47%

LRP6 modulates the phosphorylation of Cx43 via Gαs in ventricular tachycardia of myocardial infarction

Zhang

Liu²,

Cai

et al. 2022

Preprint

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“…The establishment of an enhanced vasodilatory endothelial phenotype by pregnancy through gap junctional mechanisms also extends to heightened ovine UAEC responses to cAMP by stimulating gap junctional trafficking and open gating. This effect was opposed by cGMP, however, illustrating the differential regulatory control of Cx43 gap junction function by cyclic nucleotides (119) that are, in turn, subject to regulation by placentally derived signals such as estrogen and VEGF. This is one example of how fetoplacental signals may induce endothelial plasticity in favor of vasodilation and thereby simultaneously impact both regional blood flows and total peripheral resistance.…”

Section: The Uteroplacental Circulationmentioning

confidence: 98%

Plasticity of the Maternal Vasculature During Pregnancy

Osol

Mandalà

2019

Annu. Rev. Physiol.

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Maternal cardiovascular changes during pregnancy include an expansion of plasma volume, increased cardiac output, decreased peripheral resistance, and increased uteroplacental blood flow. These adaptations facilitate the progressive increase in uteroplacental perfusion that is required for normal fetal growth and development, prevent the development of hypertension, and provide a reserve of blood in anticipation of the significant blood loss associated with parturition. Each woman’s genotype and phenotype determine her ability to adapt in response to molecular signals that emanate from the fetoplacental unit. Here, we provide an overview of the major hemodynamic and cardiac changes and then consider regional changes in the splanchnic, renal, cerebral, and uterine circulations in terms of endothelial and vascular smooth muscle cell plasticity. Although consideration of gestational disease is beyond the scope of this review, aberrant signaling and/or maternal responsiveness contribute to the etiology of several common gestational diseases such as preeclampsia, intrauterine growth restriction, and gestational diabetes.

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“…Connexins have rapid turnover rates and have been shown in other tissues, such as bone, to decrease in expression with age [ 44 ]. Additionally, it is known that cyclic nucleotides are involved in dynamic regulation of gap junction permeability and turnover [ 45 ]. It is possible that by disrupting the cGMP signaling pathway, the process of gap junction turnover and renewal is affected, leading to more greatly reduced levels in the GC1 −/− mice compared to Wt with age.…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

Holden

Awamlh

Croteau

et al. 2022

IJMS

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The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1−/−) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1−/− mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1−/− and wild type mice. GC1−/− mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1−/− mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1−/− mice.

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Cyclic Nucleotides Differentially Regulate Cx43 Gap Junction Function in Uterine Artery Endothelial Cells From Pregnant Ewes

Abstract: Supplemental Digital Content is available in the text.

Cited by 15 publications

References 31 publications

LRP6 modulates the phosphorylation of Cx43 via Gαs in ventricular tachycardia of myocardial infarction

LRP6 modulates the phosphorylation of Cx43 via Gαs in ventricular tachycardia of myocardial infarction

Plasticity of the Maternal Vasculature During Pregnancy

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

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