Pulmonary Hypertension and ATP-Sensitive Potassium Channels

McClenaghan, Conor; Woo, Kel Vin; Nichols, Colin G.

doi:10.1161/hypertensionaha.119.12992

Cited by 28 publications

(24 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…119,120 Vasoconstrictor substance (ET-1,Ang II,NE,NPY1), vasodilator substance (NO,H2S,A2, EET), translational modifier substance(PKC,PI3-AKT,PKA),mediating immune inflammatory substance (LPS,TLR3,TNF,IFN), redox substance (ROS,H2O2,GSH) and transcription inducing factor (HIF-1α, NF- κB, FOXO1) can regulate vascular tension, cell proliferation and inflammation by mediating K ATP activity. 121,122 It was found that the expression of SUR-2 and Kir6.1 was down-regulated in hypertensive rat model. 123–125 The use of K ATP channel opener iptakalim can effectively reduce PAP, right ventricular systolic pressure and pulmonary arteriole wall remodelling in the model of hypoxic PH.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of ions in pulmonary hypertension

Liu

fu²,

Tian

et al. 2021

Pulm. circ.

View full text Add to dashboard Cite

Pulmonary hypertension（PH）is a kind of hemodynamic and pathophysiological state, in which the pulmonary artery pressure (PAP) rises above a certain threshold. The main pathological manifestation is pulmonary vasoconstriction and remodelling progressively. More and more studies have found that ions play a major role in the pathogenesis of PH. Many vasoactive substances, inflammatory mediators, transcription-inducing factors, apoptosis mediators, redox substances and translation modifiers can control the concentration of ions inside and outside the cell by regulating the activity of ion channels, which can regulate vascular contraction, cell proliferation, migration, apoptosis, inflammation and other functions. We all know that there are no effective drugs to treat PH. Ions are involved in the occurrence and development of PH, so it is necessary to clarify the mechanism of ions in PH as a therapeutic target for PH. The main ions involved in PH are calcium ion (Ca2+), potassium ion (K+), sodium ion (Na+) and chloride ion (Cl–). Here, we mainly discuss the distribution of these ions and their channels in pulmonary arteries and their role in the pathogenesis of PH.

show abstract

Section: Introductionmentioning

confidence: 99%

The mechanism of ions in pulmonary hypertension

Liu

fu²,

Tian

et al. 2021

Pulm. circ.

View full text Add to dashboard Cite

show abstract

“…10 Gain of function in a different subtype causes a genetic disorder called Cantu syndrome, which manifests similarly to the side effects of diazoxide with edema, hypertrichosis, and pulmonary hypertension. 10 One can speculate that some predisposition (e.g. a K ATP channel gene mutation or overexpression) may lead to the diazoxide-associated pulmonary hypertension when stimulated by initiation of diazoxide therapy, similar to a “two-hit hypothesis” in other fields.…”

Section: Discussionmentioning

confidence: 99%

Diazoxide‐associated pulmonary hypertension in a patient with noncompaction cardiomyopathy

et al. 2021

View full text Add to dashboard Cite

Development of pulmonary hypertension after initiation of diazoxide for treatment of neonatal hyperinsulinemic hypoglycemia is a rare, but previously described association. Risk factors for development of diazoxide associated pulmonary hypertension include lower gestational age and congenital heart disease. This novel case report describes an infant with noncompaction cardiomyopathy who developed pulmonary hypertension shortly after initiation of diazoxide for hyperinsulinemic hypoglycemia which resolved upon cessation of the drug. This case highlights the benefit of having pre-treatment knowledge of underlying cardiac anatomy and makes a case for routine echocardiographic screening for neonates initiating diazoxide treatment.

show abstract

“…In hypoxia, K ATP channels are inhibited in the pulmonary smooth muscle cells, inducing Ca 2+ uptake and thus, an increase in contraction and proliferation that could start PH 18 . This would end up increasing shear stress, inducing endothelial cells to proliferate 40,41 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of rare ABCC8 variants identified in Spanish pulmonary arterial hypertension patients

Lago-Docampo

Tenorio

Hernández-González

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Pulmonary Arterial Hypertension (PAH) is a rare and fatal disease where knowledge about its genetic basis continues to increase. In this study, we used targeted panel sequencing in a cohort of 624 adult and pediatric patients from the Spanish PAH registry. We identified 11 rare variants in the ATP-binding Cassette subfamily C member 8 (ABCC8) gene, most of them with splicing alteration predictions. One patient also carried another variant in SMAD1 gene (c.27delinsGTAAAG). We performed an ABCC8 in vitro biochemical analyses using hybrid minigenes to confirm the correct mRNA processing of 3 missense variants (c.211C > T p.His71Tyr, c.298G > A p.Glu100Lys and c.1429G > A p.Val477Met) and the skipping of exon 27 in the novel splicing variant c.3394G > A. Finally, we used structural protein information to further assess the pathogenicity of the variants. The results showed 11 novel changes in ABCC8 and 1 in SMAD1 present in PAH patients. After in silico and in vitro biochemical analyses, we classified 2 as pathogenic (c.3288_3289del and c.3394G > A), 6 as likely pathogenic (c.211C > T, c.1429G > A, c.1643C > T, c.2422C > A, c.2694 + 1G > A, c.3976G > A and SMAD1 c.27delinsGTAAAG) and 3 as Variants of Uncertain Significance (c.298G > A, c.2176G > A and c.3238G > A). In all, we show that coupling in silico tools with in vitro biochemical studies can improve the classification of genetic variants.

show abstract

Pulmonary Hypertension and ATP-Sensitive Potassium Channels

Cited by 28 publications

References 146 publications

The mechanism of ions in pulmonary hypertension

The mechanism of ions in pulmonary hypertension

Diazoxide‐associated pulmonary hypertension in a patient with noncompaction cardiomyopathy

Characterization of rare ABCC8 variants identified in Spanish pulmonary arterial hypertension patients

Contact Info

Product

Resources

About