Remodelling and dysfunction of the sinus node in pulmonary arterial hypertension

Logantha, Sunil Jit RJ, Yamanushi, Tomoko T, Absi, Mais, Temple, Ian P, Kabuto, Hideaki, Hirakawa, Eiichiro, Quigley, Gillian, Zhang, X, Gurney, Alison M, Hart, George
et al (show 4 more authors) (2023) Remodelling and dysfunction of the sinus node in pulmonary arterial hypertension. PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 378 (1879). 20220178-.

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Patients with pulmonary arterial hypertension (PAH) have a high burden of arrhythmias, including arrhythmias arising from sinus node dysfunction, and the aim of this study was to investigate the effects of PAH on the sinus node. In the rat, PAH was induced by an injection of monocrotaline. Three weeks after injection, there was a decrease of the intrinsic heart rate (heart rate in the absence of autonomic tone) as well as the normal heart rate, evidence of sinus node dysfunction. In the sinus node of PAH rats, there was a significant downregulation of many ion channels and Ca<sup>2+</sup>-handling genes that could explain the dysfunction: HCN1 and HCN4 (responsible for pacemaker current, <i>I</i><sub>f</sub>), Cav1.2, Cav1.3 and Cav3.1 (responsible for L- and T-type Ca<sup>2+</sup> currents, <i>I</i><sub>Ca,L</sub> and <i>I</i><sub>Ca,T</sub>), NCX1 (responsible for Na<sup>+</sup>-Ca<sup>2+</sup> exchanger) and SERCA2 and RYR2 (Ca<sup>2+</sup>-handling molecules). In the sinus node of PAH rats, there was also a significant upregulation of many fibrosis genes that could also help explain the dysfunction: vimentin, collagen type 1, elastin, fibronectin and transforming growth factor β1. In summary, in PAH, there is a remodelling of ion channel, Ca<sup>2+</sup>-handling and fibrosis genes in the sinus node that is likely to be responsible for the sinus node dysfunction. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Item Type: Article
Uncontrolled Keywords: pulmonary arterial hypertension, heart failure, sinus node, ion channels, cardiac remodelling
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 23 May 2023 08:04
Last Modified: 14 Jun 2023 18:56
DOI: 10.1098/rstb.2022.0178
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