Catestatin reverses the hypertrophic effects of norepinephrine in H9c2 cardiac myoblasts by modulating the adrenergic signaling

Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

“…The same study revealed that CST levels did not differ in respect to LVEF phenotypes while CST levels independently correlated with NYHA class, waist-to-hip ratio, HbA1c, LDL cholesterol, non-HDL cholesterol, high sensitivity cardiac troponin I and the heart rate at admission and rest. Finally, higher CST levels were strongly associated with favorable echocardiographic profile as they positively correlated with smaller LV volumes and dimensions, as well as with decreased left ventricular mass and smaller dimensions of the left atrium and this finding clinically validates the concept that CST locally has cardioprotective effects, attenuates adverse ventricular remodeling and acts in antihypertrophic fashion, as these biological effects were postulated in a few earlier preclinical studies[ 307 , 315 ].…”

“…Of established cardiovascular effects, CST suppresses beta-adrenergic activation and acts in a negative inotropic and chronotropic fashion, stimulates angiogenesis and proliferation of vascular smooth muscle cells, decreases thrombogenicity of endothelial cells, suppresses atherosclerosis and inflammation while also exerts cardioprotective effects by abrogating cardiomyocyte ischemia-reperfusion injury[ 299 - 306 ]. A very recent study by Alam et al[ 307 ] showed that CST has a direct and independent inhibiting effect on hypertrophy elicited by NE in the cultured H9c2 cardiac myoblasts and that is involved in the regulation of a large number of fetal genes that are upregulated during the process of myocardial hypertrophy[ 307 ]. Furthermore, the same study showed that CST effectively blunted stimulative effects of NE and other mitogenic signals on β 1 and β 2 adrenergic receptors thus providing novel evidence that CST has a direct modulatory effect on adrenergic transmission at the level of adrenergic receptors.…”

Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT‐HF study

“…21 Even more, CST directly and locally modulates adrenergic signalling by abolishing the adverse effects of norepinephrine at the level of β 1 and β 2 adrenergic receptors in cardiac myoblasts. 22 Our previous study showed that levels of CST were significantly higher among ADHF patients with ischaemic aetiology of the syndrome than those with non-ischaemic aetiologies and among patients that had more severe symptoms. 16 These increased CST levels were most likely observed as the compensatory mechanism to increased sympathetic activation that, in the decompensated HF stage and especially among those with established ischaemic disease and advanced symptoms, significantly overpowers neurohormonal pathways that exert cardioprotective effects.…”

“…It acts as a potent catecholamine release inhibitor by binding to the neuronal nicotinic acetylcholine receptor thereby blunting the exocytosis of neurohormones including catecholamines and also exerts direct vasodilatative and hypotensive effects through stimulation of histamine release from mast cells via heterotrimeric G‐protein signalling 21 . Even more, CST directly and locally modulates adrenergic signalling by abolishing the adverse effects of norepinephrine at the level of β 1 and β 2 adrenergic receptors in cardiac myoblasts 22 . Our previous study showed that levels of CST were significantly higher among ADHF patients with ischaemic aetiology of the syndrome than those with non‐ischaemic aetiologies and among patients that had more severe symptoms 16 .…”

Serum Catestatin Levels and Arterial Stiffness Parameters Are Increased in Patients with Inflammatory Bowel Disease

“…Since the physiological effects of norepinephrine and SNS mediators promote tachyphylaxis and systemic vasoconstriction it is possible that these effects contributed to detrimental vascular remodeling as evident in increased arterial stiffness parameters. Finally, although CST stand-alone generally confers protective effects on heart and vasculature, as shown in a handful of previous studies [22,23,60,61], it is possible that in the setting of IBD, a disease state characterized by persistent inflammation and increased SNS activity, effects of CST, despite being elevated in circulation, are not sufficient to compensate for adverse arterial remodeling that is propagated by the proinflammatory and adrenergic cellular pathways. However, due to a substantial evidence gap in this regard and lack of studies reporting on CST and arterial stiffness parameters, these hypothetical interactions need to be confirmed in future preclinical and mechanistic studies.…”