Transcriptomic profile of cationic channels in human pulmonary arterial hypertension

AbstractThe dysregulation of K+ channels is a hallmark of pulmonary arterial hypertension (PAH). Herein, the channelome was analyzed in lungs of patients with PAH in a public transcriptomic database. Sixty six (46%) mRNA encoding cationic channels were dysregulated in PAH with most of them downregulated (83%). The principal component analysis indicated that dysregulated cationic channel expression is a signature of the disease. Changes were very similar in idiopathic, connective tissue disease and congenital heart disease associated PAH. This analysis 1) is in agreement with the widely recognized pathophysiological role of TASK1 and KV1.5, 2) supports previous preliminary reports pointing to the dysregulation of several K+ channels including the downregulation of KV1.1, KV1.4, KV1.6, KV7.1, KV7.4, KV9.3 and TWIK2 and the upregulation of KCa1.1 and 3) points to other cationic channels dysregulated such as Kv7.3, TALK2, CaV1 and TRPV4 which might play a pathophysiological role in PAH. The significance of other changes found in Na+ and TRP channels remains to be investigated.

Download Full-text

Possible pathophysiological role of vitamin D deficit in pulmonary arterial hypertension

10.1183/13993003.congress-2018.pa3083 ◽

2018 ◽

Cited By ~ 1

Author(s):

Maria Callejo ◽

Daniel Morales-Cano ◽

Gema Mondejar-Parreño ◽

Bianca Barreira ◽

Sergio Esquivel-Ruiz ◽

...

Keyword(s):

Vitamin D ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Pathophysiological Role ◽

Pulmonary Arterial

Download Full-text

The pathophysiological role of novel pulmonary arterial hypertension gene SOX17

European Respiratory Journal ◽

10.1183/13993003.04172-2020 ◽

2021 ◽

pp. 2004172

Author(s):

Yukyee Wu ◽

John Wharton ◽

Rachel Walters ◽

Eleni Vasilaki ◽

Jurjan Aman ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Dominant Mode ◽

Pulmonary Vasculature ◽

Incomplete Penetrance ◽

Pathophysiological Role ◽

Sequencing Studies ◽

Pulmonary Arterial ◽

The Right

Pulmonary arterial hypertension (PAH) is a progressive disease predominantly targeting pre-capillary blood vessels. Adverse structural re-modelling and increased pulmonary vascular resistance result in cardiac hypertrophy and ultimately failure of the right ventricle. Recent whole genome and exome sequencing studies have identified SOX17 as a novel risk gene in PAH, with a dominant mode of inheritance and incomplete penetrance. Rare deleterious variants in the gene and more common variants in upstream enhancer sites have both been associated with the disease and a deficiency of SOX17 expression may predispose to PAH. This review aims to consolidate the evidence linking genetic variants in SOX17 to PAH and explores the numerous targets and effects of the transcription factor, focussing on the pulmonary vasculature and the pathobiology of PAH.

Download Full-text

The Essential Role of Imaging in the Evaluation of Patients With Pulmonary Arterial Hypertension in Association With Congenital Heart Disease

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-11.4.171 ◽

2013 ◽

Vol 11 (4) ◽

pp. 171-182

Author(s):

Giancarlo Scognamiglio ◽

Sonya V. Babu-Narayan ◽

Michael B. Rubens ◽

Michael A. Gatzoulis ◽

Wei Li

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Congenital Heart ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Pulmonary Arterial ◽

The Individual

Pulmonary arterial hypertension (PAH) is a hemodynamic and pathophysiologic condition defined as an increase in mean pulmonary artery pressure (MPAP) of ≥25 mm Hg at rest measured at right heart catheterization (RHC).12 Patients with PAH associated with congenital heart disease (PAH-CHD) are a growing population consisting of an anatomically and phenotypically heterogeneous group, where differences among specific cardiac defects, along with their varied clinical course and prognosis, influence treatment choices for the individual patient.

Download Full-text