Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Abstract

Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.

Transcriptomic Validation of the Protective Effects of Aqueous Bark Extract of Terminalia arjuna (Roxb.) on Isoproterenol-Induced Cardiac Hypertrophy in Rats

“…The mechanisms of adrenoceptor activation, its downstream targets, its signal specificity versus bias and receptor dynamics have been extensively studied for understanding the role of adrenergic system in cardiovascular pathophysiology (Lohse, 2015). Also, the cross talk between adrenergic signaling and that by other receptor viz., insulin, EGF and TGFβ play a critical role in cardiovascular function (Saha et al, 2012;Heger et al, 2016;Fu et al, 2017;Mohan et al, 2017). Signaling by these receptors in heart involve a plethora of kinases, phosphatases, second messengers and gene regulatory proteins.…”

Cardiac Contractility Modulation in Heart Failure Patients. Fundamental Mechanisms and Clinical Results

“…Во многих исследованиях, посвященных механизмам ремоделирования сердца, показано, что трансформирующий ростовой фактор бета (TGF-β1) играет важную роль в патогенезе миокардиального фиброза, усиливая синтез экстрацеллюлярного матрикса и замедляя его деградацию [34]. Smad3 является ключевым медиатором сигнального пути TGF-β1 при различных патологических состояниях [35].…”

Loss of nuclear ARC contributes to the development of cardiac hypertrophy in rats

“…Sustained cardiac hypertrophy is often accompanied by maladaptive remodelling and induced myocardial stiffness, which accelerates heart failure. [4][5][6][7] Signalling pathways that underlie cardiac hypertrophy have been extensively investigated. 3 Furthermore, these two processes share several common stimuli and regulators.…”

“…For instance, adrenaline, angiotensin and tumour necrosis factor-α have been proved to be key regulators and to induce both cardiac hypertrophy and apoptosis. [4][5][6][7] Signalling pathways that underlie cardiac hypertrophy have been extensively investigated. However, despite the growing number of inducers that have been identified, few inhibitors have been found.…”