The alpha1-adrenergic receptors in cardiac hypertrophy: Signaling mechanisms and functional implications

Cotecchia, Susanna; Vescovo, Cosmo Damiano del; Colella, Matilde; Caso, Stefania; Diviani, Dario

doi:10.1016/j.cellsig.2015.06.009

Cited by 46 publications

(36 citation statements)

References 123 publications

(166 reference statements)

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“…Recent evidence is suggesting a cardioprotective role of α1-adrenergic receptors in the heart function in congestive heart failure (in the ALLHAT clinical trial, the arm of the trial using α1-blocker doxazosin had to be stopped because of higher number of heart failure events) (Cotecchia et al, 2015). Thus, the role and mechanisms of the “augmented of α-adrenergic tone in heart failure” (Leier et al, 1990) needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

et al. 2017

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Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades.Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fisher's Method to combine the p-value of multiple tests.Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades.Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases.

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Section: Discussionmentioning

confidence: 99%

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

et al. 2017

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“…Cardiac hypertrophy increases cardiomyocyte size and myocardial mass in response to physiological or pathological events that also induce remodeling [65]. Myocyte hypertrophy is a key factor in the transition from a normal to a pathologic heart in alcohol-induced and other causes of heart damage [28,66].…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

“…Myocyte hypertrophy is a key factor in the transition from a normal to a pathologic heart in alcohol-induced and other causes of heart damage [28,66]. However, cardiac hypertrophy may also be an adaptive mechanism to stressful conditions of the heart, but prolonged hypertrophy may lead to cardiac dysfunction and heart failure which represents the primary cause of human morbidity and mortality [65,67]. According to the Frank–Starling law, mechanical overload to the ventricle is compensated with chamber enlargement [66,68].…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

“…Indeed, the signaling events of this receptor contribute to the definition of molecular and cellular cardiac features [65,79]. New hypotheses have emerged concerning the functional role of α1-AR receptors in the heart.…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

“…New hypotheses have emerged concerning the functional role of α1-AR receptors in the heart. Regulation of these receptors may modify cardiac hypertrophy [65]. Thus, endogenous BNP attenuates cardiomyocyte hypertrophy induced by Ang II via the p38 MAPK/Smad signaling pathway [80,81].…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

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New Treatment Strategies for Alcohol-Induced Heart Damage

Fernández‐Solà

Porta

2016

IJMS

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High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use.

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Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation

et al. 2022

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Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐endocrine substances like catecholamines or the renin‐angiotensin‐aldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen‐activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt‐GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P < 0.05) and in mouse ejecting hearts (AKT 51%, GSK49%, P < 0.05), whereas phosphorylation of MAPKs was not influenced by increased preload. Selective elevation of afterload revealed an increase in ERK phosphorylation in the ejecting heart (43%, P < 0.05), but not in AKT, GSK3β, and the other MAPKs. Elevation of preload and afterload in the ejecting heart induced a significant phosphorylation of ERK (95%, P < 0.001) and showed a moderate increased AKT (P = 0.14) and GSK3β (P = 0.21) phosphorylation, which did not reach significance. Preload and afterload elevation in muscles strips from human failing hearts showed neither AKT nor ERK phosphorylation changes. Conclusions Our data show that preload activates the AKT–GSK3β and afterload the ERK pathway in vitro, indicating an intrinsic mechanism independent of endocrine signalling.

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The alpha1-adrenergic receptors in cardiac hypertrophy: Signaling mechanisms and functional implications

Cited by 46 publications

References 123 publications

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

New Treatment Strategies for Alcohol-Induced Heart Damage

Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation

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