Overexcited MaxiK and KATP channels underlie obstructive jaundice-induced vasoconstrictor hyporeactivity of arterial smooth muscle

Yuan, Yawei; Wang, Long; Lu, Zhan-ying; Long, Yunfei; Jiao, Yingfu; Xia, Qiang; Wen, Daxiang; Yu, Weifeng

doi:10.1038/srep39246

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…It has been reported that BDL-induced cirrhosis alters the expression level of ion channels such as voltage-dependent Na + channels ( Lee et al, 2016 ), epithelial Na + channels ( Kim et al, 2006 ), large-conductance K Ca (BK Ca ) channels ( Yuan et al, 2016 ; Jadeja et al, 2017 ), ATP-sensitive K + channels ( Yuan et al, 2016 ), transient receptor potential canonical subfamily (TRPC) channels ( Nedungadi and Cunningham, 2014 ; Jadeja et al, 2017 ), and transient receptor potential vanilloid subfamily (TRPV) channels ( Nedungadi et al, 2012 ; Belghiti et al, 2013 ; Hong-Qian Wang et al, 2019 ). In addition, we noted the downregulation of TMEM16A (and also TMEM16F) expression in cirrhotic BDL mice, but not in non-cirrhotic PPVL mice.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

et al. 2022

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Portal hypertension is defined as an increased pressure in the portal venous system and occurs as a major complication in chronic liver diseases. The pathological mechanism underlying the pathogenesis and development of portal hypertension has been extensively investigated. Vascular tone of portal vein smooth muscles (PVSMs) is regulated by the activities of several ion channels, including Ca2+-activated Cl− (ClCa) channels. TMEM16A is mainly responsible for ClCa channel conductance in vascular smooth muscle cells, including portal vein smooth muscle cells (PVSMCs). In the present study, the functional roles of TMEM16A channels were examined using two experimental portal hypertensive models, bile duct ligation (BDL) mice with cirrhotic portal hypertension and partial portal vein ligation (PPVL) mice with non-cirrhotic portal hypertension. Expression analyses revealed that the expression of TMEM16A was downregulated in BDL-PVSMs, but not in PPVL-PVSMs. Whole-cell ClCa currents were smaller in BDL-PVSMCs than in sham- and PPVL-PVSMCs. The amplitude of spontaneous contractions was smaller and the frequency was higher in BDL-PVSMs than in sham- and PPVL-PVSMs. Spontaneous contractions sensitive to a specific inhibitor of TMEM16A channels, T16Ainh-A01, were reduced in BDL-PVSMs. Furthermore, in normal PVSMs, the downregulation of TMEM16A expression was mimicked by the exposure to angiotensin II, but not to bilirubin. This study suggests that the activity of ClCa channels is attenuated by the downregulation of TMEM16A expression in PVSMCs associated with cirrhotic portal hypertension, which is partly mediated by increased angiotensin II in cirrhosis.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

et al. 2022

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“…The agonist activity on the bile acid receptors may represent a link between gut microbiota and the cardiovascular system (169). In addition to the dose-dependent vasorelaxation, bile acids also modulate the transcription of vasoactive molecules by targeting transcription factor FXR, representing an additional mechanism for bile acids effects on cardiovascular function (175).…”

Section: Secondary Bile Acidsmentioning

confidence: 99%

“…Altogether, these data show that bile acids are involved in CVD progression and in ethanol-induced gut microbiota alterations. In this context, a link between cholestasis and cardiovascular dysfunction has been proposed (175). Ethanol consumption leads to cholestasis (114,172,173,176), characterized by increased bile salt retention (176).…”

Section: Secondary Bile Acidsmentioning

confidence: 99%

Ethanol: striking the cardiovascular system by harming the gut microbiota

Silva

Elias-Oliveira

McCarthy

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

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Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The crosstalk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.

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“…Analogous to miRNAs, piRNAs are stable in biofluids such as plasma and blood [ 170 ]. piRNAs isolated from these biofluids were found to be deregulated in patients with colorectal cancer, prostate cancer, and pancreatic cancer [ 171 ]. More studies confirming the prognostic potential of circulating piRNAs may add a new dimension to the existing roles of piRNAs.…”

Section: Piwi-interacting Rnas (Pirnas)mentioning

confidence: 99%

The Challenges and Opportunities in the Clinical Application of Noncoding RNAs: The Road Map for miRNAs and piRNAs in Cancer Diagnostics and Prognostics

Krishnan

Damaraju

2018

International Journal of Genomics

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Discoveries on nonprotein-coding RNAs have induced a paradigm shift in our overall understanding of gene expression and regulation. We now understand that coding and noncoding RNA machinery work in concert to maintain overall homeostasis. Based on their length, noncoding RNAs are broadly classified into two groups—long (>200 nt) and small noncoding RNAs (<200 nt). These RNAs perform diverse functions—gene regulation, splicing, translation, and posttranscriptional modifications. MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) are two classes of small noncoding RNAs that are now classified as master regulators of gene expression. They have also demonstrated clinical significance as potential biomarkers and therapeutic targets for several diseases, including cancer. Despite these similarities, both these RNAs are generated through contrasting mechanisms, and one of the aims of this review is to cover the distance travelled since their discovery and compare and contrast the various facets of these RNAs. Although these RNAs show tremendous promise as biomarkers, translating the findings from bench to bedside is often met with roadblocks. The second aim of this review therefore is to highlight some of the challenges that hinder application of miRNA and piRNA as in guiding treatment decisions.

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Overexcited MaxiK and KATP channels underlie obstructive jaundice-induced vasoconstrictor hyporeactivity of arterial smooth muscle

Cited by 6 publications

References 32 publications

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

Downregulation of Ca2+-Activated Cl− Channel TMEM16A Mediated by Angiotensin II in Cirrhotic Portal Hypertensive Mice

Ethanol: striking the cardiovascular system by harming the gut microbiota

The Challenges and Opportunities in the Clinical Application of Noncoding RNAs: The Road Map for miRNAs and piRNAs in Cancer Diagnostics and Prognostics

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