New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling

Htet, Myo; Nally, Jane E.; Martin, Patricia; Dempsie, Yvonne

doi:10.3390/ijms23010379

Cited by 6 publications

(2 citation statements)

References 75 publications

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“…However, in contrast with HTN, much less is known about cardiac Cx43 alterations in PAH. Nevertheless, available data suggest the pathogenic implication of Cx43 not only in the heart muscle but also in pulmonary vessels [ 28 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Sykora,

Szeiffova Bacova,

Andelova

et al. 2024

IJMS

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While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function.

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Section: Introductionmentioning

confidence: 99%

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Sykora,

Szeiffova Bacova,

Andelova

et al. 2024

IJMS

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“…Several studies have reported independent and GJ-dependent roles of cxs in mediating angiogenesis in various disorders (2,3). Although there are a few reviews on the role of cxs in various physiological processes (4)(5)(6)(7)(8)(9), there is little discussion of how Cxs influence the angiogenic process involved in wound repair, tumorigeneses, and cardiovascular disorders. The purpose of the present study was to examine the current state of knowledge regarding cx structure, nomenclature, function, and regulation, as well as the newly identified link between cxs and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review)

et al. 2022

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connexins (cxs) play key roles in cellular communication. By facilitating metabolite exchange or interfering with distinct signaling pathways, cxs affect cell homeostasis, proliferation, and differentiation. Variations in the activity and expression of cxs have been linked to numerous clinical conditions including carcinomas, cardiac disorders, and wound healing. Recent discoveries on the association between cxs and angiogenesis have sparked interest in cx-mediated angiogenesis due to its essential functions in tissue formation, wound repair, tumor growth, and metastasis. It is now widely recognized that understanding the association between cxs and angiogenesis may aid in the development of new targeted therapies for angiogenic diseases. The aim of the present review was to provide a comprehensive overview of cxs and cx-mediated angiogenesis, with a focus on therapeutic implications. Contents1. Introduction 2. Methodology 3. cxs, diseases and potential therapies 4. conclusions and future directions

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Therapeutic potential of carbon monoxide in hypertension-induced vascular smooth muscle cell damage revisited: From physiology and pharmacology

Sun

Wang

Nie

et al. 2022

Biochemical Pharmacology

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New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling

Cited by 6 publications

References 75 publications

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension

Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review)

Therapeutic potential of carbon monoxide in hypertension-induced vascular smooth muscle cell damage revisited: From physiology and pharmacology

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