Role of connexin 43 in cardiovascular diseases

Pecoraro, Michela; Velia, Verrilli; Pinto, Aldo; Popolo, Ada

doi:10.1016/j.ejphar.2015.10.030

Cited by 136 publications

(130 citation statements)

References 58 publications

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“…A recent study showed that miR-1298 inhibits connexin-43 expression and vascular smooth muscle cell proliferation and migration (26). Connexin-43, a gap junction protein, is required for maintenance of the normal cardiac rhythm, regulation of vascular tone, and endothelial function (42). Since miR-1298 increased in the hypertrophic RV but not in the LV, we suggest that miR-1298-mediated decrease of connexin-43 could be one of the causes of arrhythmia and impaired coronary artery function in the right heart of PAH rats.…”

Section: H696mentioning

confidence: 99%

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

Joshi

Dhagia

Gairhe

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Joshi SR, Dhagia V, Gairhe S, Edwards JG, McMurtry IF, Gupte SA. MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 311: H689 -H698, 2016. First published July 15, 2016 doi:10.1152/ajpheart.00264.2016.-Heart failure, a major cause of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), is an outcome of complex biochemical processes. In this study, we determined changes in microRNAs (miRs) in the right and left ventricles of normal and PAH rats. Using an unbiased quantitative miR microarray analysis, we found 1) miR- 21-5p, miR-31-5 and 3p, miR-140-5 and 3p, miR-208b-3p, miR-221-3p, miR-222-3p, miR-702-3p, and miR-1298 were upregulated (Ͼ2-fold; P Ͻ 0.05) in the right ventricle (RV) of PAH compared with normal rats; 2) miR-31-5 and 3p, and miR-208b-3p were upregulated (Ͼ2-fold; P Ͻ 0.05) in the left ventricle plus septum (LVϩS) of PAH compared with normal rats; 3) miR-187-5p, miR-208a-3p, and miR-877 were downregulated (Ͼ2-fold; P Ͻ 0.05) in the RV of PAH compared with normal rats; and 4) no miRs were up-or downregulated with Ͼ2-fold in LVϩS compared with RV of PAH and normal. Upregulation of miR-140 and miR-31 in the hypertrophic RV was further confirmed by quantitative PCR. Interestingly, compared with control rats, expression of mitofusin-1 (MFN1), a mitochondrial fusion protein that regulates apoptosis, and which is a direct target of miR-140, was reduced in the RV relative to LVϩS of PAH rats. We found a correlation between increased miR-140 and decreased MFN1 expression in the hypertrophic RV. Our results also demonstrated that upregulation of miR-140 and downregulation of MFN1 correlated with increased RV systolic pressure and hypertrophy. These results suggest that miR-140 and MFN1 play a role in the pathogenesis of PAH-associated RV dysfunction.Listen to this article's corresponding podcast at http://ajpheart. podbean.com/e/mir140-and-right-heart-hypertrophy/. miR; heart; hypertrophy; heart failure; pulmonary; hypertension; lungs; rats THE PATHOPHYSIOLOGY of pulmonary arterial hypertension (PAH) is heterogeneous. In PAH, pulmonary vascular resistance and arterial pressure are increased, and the right ventricle (RV) is hypertrophied in response to increased afterload/pressure overload. Increased afterload in PAH leads to myocardial dysfunction, tricuspid regurgitation with progressive annular dilatation, and ultimately RV failure (67).Heart failure, a major cause of mortality in PAH patients (4, 5), is a complex syndrome. In the failing hearts, oxidative stress is increased and the rate of cardiomyocyte apoptotic and autophagic death is augmented (6,49,51,60,62). Activation of these processes causes myocardial stiffening, dilatation, and loss of contractility (49, 51). However, the mechanisms that regulate apoptosis and autophagy in this complex pathology are unclear and are an area under investigation.MicroRNAs (miRs) are a class of small no...

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Section: H696mentioning

confidence: 99%

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

Joshi

Dhagia

Gairhe

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…Hence, it could be concluded that loureirin B might promote insulin secretion due to inhibiting of KATP channels and the influx of Ca 2+ to the intracellular. As one of the important connexin, Cx43 plays an important role in mediating the flow of ions and small molecules such as K + and Ca 2+ [24]. In our study, the expression of Cx43 protein was also detected.…”

Section: Discussionmentioning

confidence: 48%

“…As one of the important connexin, Cx43 plays an important role in mediating the flow of ions, such as K + and Ca 2+ [15]. In this study, the expression of Cx43protein was detected (Fig.…”

Section: Effect Of Loureirin B On the Current Of K Atp Channelmentioning

confidence: 83%

“…Therefore, the change of KATP current on Ins-1 cells and the intracellular Ca 2+ levels were detected. What's more, the expression of Cx43 protein was employed because it played an important role in mediating the flow of ions, such as K + and Ca 2+ [14,15]. Based on computational methods and experiments in vitro, we investigated the mechanism of loureirin B how it could promote insulin secretion and proposed the hypothesis that loureirin B had an effect on insulin secretion of pancreatic β-cells, the current of KATP channel, the increase [Ca 2+ ]i and the expression of Cx43 protein (Fig.1).…”

Section: Introductionmentioning

confidence: 99%

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Insulin Secretion with the Effect of Loureirin B through K<sub>ATP </sub>Channel–Dependent Pathway

Sha¹,

Zhang²,

Cao³

et al. 2017

Preprint

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The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For understanding the mechanism, a series of experiments had been employed based on computational methods and cell experiments. The insulin secretion significantly increased with the incubation of 0.01μM loureirin B for 4 hours. The viability of Ins-1 cells showed no significant difference with the treatment of loureirin B. Through computational methods, we hypothesized that loureirin B could interacts with KATP channels to promote insulin secretion. In cell experiments, it could be found that the current of KATP channel of Ins-1 cells was inhibited by the effect of loureirin B. After then, the voltage-dependent calcium channels were activated, the increase of Cx43 protein expression might mediate the Ca 2+ to the intracellular. In summary, it could be concluded that loureirin B promoted insulin secretion mainly through inhibiting KATP current, the influx of Ca 2+ to the Intracellular and the expression of Cx43.

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“…Gap junctions also promote intercellular communication in the cardiovascular system and are essential for normal vascular function [13,14]. Connexins expressed in the vascular wall include Cx37, Cx40, Cx43, and Cx45 and those expressed by endothelial cells include Cx37 and Cx40 [12,14].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Human Aortic Endothelial Cells, Endothelial Progenitor Cells, and Cardiomyocytes

Chen¹,

Kuo²

2017

J Tradi Med Clin Natur

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Despite advances in therapy, heart failure remains a significant disease burden, with poor outcomes, worldwide. Reactive Oxygen Species (ROS) damage cardiomyocytes. Endothelial progenitor cells promote the repair of the endothelium of arteries damaged by ROS. However, gene expression profiles of Human Aortic Endothelial Cells (HAECs), Endothelial Progenitor Cells (HEPCs), and Cardiomyocytes (HCMs) are unclear. In the present study, we determined the expression profiles of different genes in HAECs, HEPCs, and HCMs by performing quantitative PCR. Results showed that p53 and Cx37 were up-regulated, but VEGF, Cx43, and eNOS were down-regulated in HEPCs. Cx40 and eNOS were up-regulated in HAECs. Moreover, we determined the effect of hydrogen peroxide-derived ROS on HCMs. Results showed that Cx40, Cx45, VCAM-1, ICAM-1, p53, and p21 were up-regulated, but E-cadherin was down-regulated after high concentration of hydrogen peroxide treatment.

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Role of connexin 43 in cardiovascular diseases

Cited by 136 publications

References 58 publications

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

Insulin Secretion with the Effect of Loureirin B through K<sub>ATP </sub>Channel–Dependent Pathway

Characterization of Human Aortic Endothelial Cells, Endothelial Progenitor Cells, and Cardiomyocytes

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Role of connexin 43 in cardiovascular diseases

Cited by 136 publications

References 58 publications

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension.

Insulin Secretion with the Effect of Loureirin B through K<sub>ATP </sub>Channel&ndash;Dependent Pathway

Characterization of Human Aortic Endothelial Cells, Endothelial Progenitor Cells, and Cardiomyocytes

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Insulin Secretion with the Effect of Loureirin B through K<sub>ATP </sub>Channel–Dependent Pathway