Sympatho-adrenergic mechanisms in heart failure: new insights into pathophysiology

Abstract

The sympathetic nervous system is activated in the setting of heart failure (HF) to compensate for hemodynamic instability. However, acute sympathetic surge or sustained high neuronal firing rates activates β-adrenergic receptor (βAR) signaling contributing to myocardial remodeling, dysfunction and electrical instability. Thus, sympatho-βAR activation is regarded as a hallmark of HF and forms pathophysiological basis for β-blocking therapy. Building upon earlier research findings, studies conducted in the recent decades have significantly advanced our understanding on the sympatho-adrenergic mechanism in HF, which forms the focus of this article. This review notes recent research progress regarding the roles of cardiac β2AR or α1AR in the failing heart, significance of β1AR-autoantibodies, and βAR signaling through G-protein independent signaling pathways. Sympatho-βAR regulation of immune cells or fibroblasts is specifically discussed. On the neuronal aspects, knowledge is assembled on the remodeling of sympathetic nerves of the failing heart, regulation by presynaptic α2AR of NE release, and findings on device-based neuromodulation of the sympathetic nervous system. The review ends with highlighting areas where significant knowledge gaps exist but hold promise for new breakthroughs.

Effectiveness of Social Problem-Solving Skills Training on the Depression in Systolic Heart Failure Patients in Kermanshah

“…Charney et al (38), and Golden et al (39) found that therapy with anti-depressive drugs decreases plasma and urinary tract levels of norepinephrine and its metabolites. Du (40) revealed that heart failure is associated with the intense activation of the sympathetic nervous system. This factor plays a vital role in the progression of heart failure, and activation of the nervous and hormonal systems can worsen the heart rate and cause vascular spasms and sodium retention.…”

Cell–cell crosstalk in the heart

“…The adrenergic signaling in heart failure is traditionally investigated in cardiomyocytes. Dr. Du comprehensively summarizes the recent research on sympatho-adrenergic system in heart failure [ 14 ]. One of the major recent advances for heart failure research is the role of β-adrenergic signaling in immune cells and fibroblasts in addition to cardiomyocytes.…”

Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

“…A hyperactivation of β-adrenoreceptors of rat cardiomyocytes by ISO in high doses leads to left ventricular dysfunction with ballooning and ischemia-reperfusion injury, which is known to involve oxidative stress, proinflammatory responses, calcium overload, mitochondrial malfunction, and, ultimately, cell death [10][11][12]. Nevertheless, the subcellular mechanisms involved in ISO-induced acute ischemic damage beyond adrenergic overstimulation are still poorly understood [13,14]. Although alterations in mitochondrial function have been identified [10,12,15,16], they have not been thoroughly studied, especially in the acute period.…”