Signalling in cardiac disease: the molecular deficit at the heart of the problem

See article by Yoshida et al. [3] (pages 34–45) in this issue. Events leading to heart failure are characterized by a prolonged action potential and a deficit in cardiac performance which is paralleled by ionic remodelling and a loss of contractile function at the level of the single cardiomyocyte (see Ref. [1] for review). Increased sympathetic stimulation as well as a number of paracrine and autocrine factors lead to cardiac hypertrophy and an eventual decompensated failing phenotype [2]. However, several issues remain to be resolved in terms of a molecular mechanism for these events. First, is there a deficit in the contractile apparatus of the failing myocyte per se? Alternatively, are signalling pathways which modulate contractility and are known to be altered in the failing heart the trigger for these events? Further, the focus of work on whole cardiac tissue to date has not resolved the role of non-myocyte cells in the disease process. Finally, the subcellular localization and compartmentalization of signalling pathways and the proteins they modulate may be of critical importance as well. The study by Yoshida et al. [3] in this issue of Cardiovascular Research begins to address some of these important issues. The authors demonstrate that although contractile function is clearly maintained in isolated cardiomyocytes from animals with coronary artery ligation-induced congestive heart failure (CHF), their regulation by the β-adrenergic system is significantly altered resolving a dilemma in the literature about the actual deficit in failing hearts. Further, they show alterations in levels of Gsα but not Giα subunits in cardiomyocytes, while in non-myocytes there are significant alterations in both subtypes. These results are important as they address the actual site of the molecular deficit in cardiac tissue. The regulation of [Ca2+]i plays a central role in cardiac performance. Ca2+-dependent … * Tel.: +1-514-376-3330; fax: +1-514-376-1355 hebertt{at}icm.umontreal.ca

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.