Recombinant N–terminal fragments of chromogranin–A modulate cardiac function of the Langendorff–perfused rat heart

Cerra, Maria Carmela; Iuri, L. De; Angelone, Tommaso; Corti, Angelo; Tota, Bruno

doi:10.1007/s00395-005-0547-2

Cited by 70 publications

(94 citation statements)

References 31 publications

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“…Therefore, it has been suggested that VSs, in addition to their vasoinhibitory properties, are cardioregulatory mediators; i.e., they are able to exert an antiadrenergic action that could protect the heart against intense excitatory stimulations, such as those elicited by the stress response (9,11,19,26).…”

Section: Discussionmentioning

confidence: 99%

“…All drug-containing solutions were prepared fresh before the experiments. We used recombinant human VS-1 [STA-CgA-(1-78)] containing the VS-1 peptide (1-76) previously described (9). The rat CgA sequence is identical in that region to the human sequence.…”

Section: Animalsmentioning

confidence: 99%

“…Recently, VS-1 and VS-2 have been shown to be important protective modulators of cardiac activity because of their ability to counteract the adrenergic signals (9,18). The negative inotropism exerted by VS-1, even with different mechanisms, has been observed in several vertebrate species.…”

mentioning

confidence: 99%

“…Moreover, in eel and frog heart, changes in cytoskeletal dynamics seem to play a crucial role in the negative inotropic effect of VS-1 (22). In the isolated rat heart, VS-1, but not VS-2, elicits a dose-dependent negative inotropism under basal conditions, but both peptides abolish the isoproterenol (Iso)-induced positive inotropism without modifying the ␤-adrenergic-dependent coronary dilatation or the ouabain-induced positive inotropism (9).…”

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confidence: 99%

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Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

Gallo

Levi²,

Ramella³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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G. Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium. Am J Physiol Heart Circ Physiol 292: H2906 -H2912, 2007. First published February 9, 2007 doi:10.1152/ajpheart.01253.2006 are vasoactive peptides derived from chromogranin A (CgA), a protein contained in secretory granules of chromaffin and other cells. The negative inotropic effect and the reduction of isoproterenol (Iso)-dependent inotropism induced by VSs in the heart suggest that they have an antiadrenergic function. However, further investigation of the mechanisms of action of VSs is needed. The aim of the present study was to define the signaling pathways activated by VS-1 in mammalian ventricular myocardium and cultured endothelial cells that lead to the modulation of cardiac contractility. Ca 2ϩ and nitric oxide (NO) fluorometric confocal imaging was used to study the effects induced by recombinant human VS-1 [STA-CgA-(1-76)] on contractile force, L-type Ca 2ϩ current, and Ca 2ϩ transients under basal conditions and after ␤-adrenergic stimulation in rat papillary muscles and ventricular cells and the effects on intracellular Ca 2ϩ concentration and NO production in cultured bovine aortic endothelial (BAE-1) cells. VS-1 had no effect on basal contractility of papillary muscle, but the effect of Iso stimulation was reduced by 27%. Removal of endocardial endothelium and inhibition of NO synthesis and phosphatidylinositol 3-kinase (PI3K) activity abolished the antiadrenergic effect of VS-1 on papillary muscle. In cardiomyocytes, 10 nM VS-1 was ineffective on basal and Iso (1 M)-stimulated L-type Ca 2ϩ current and Ca 2ϩ transients. In BAE-1 cells, VS-1 induced a Ca 2ϩ -independent increase in NO production that was blocked by the PI3K inhibitor wortmannin. Our results suggest that the antiadrenergic effect of VS-1 is mainly due to a PI3K-dependent NO release by endothelial cells, rather than a direct action on cardiomyocytes. calcium channel; myocardial contractility; peptide hormones; endothelial cell CHROMOGRANIN A (CgA) and chromogranin B have long been proposed to control the physiological process of secretory granule formation because of their pH-, Ca 2ϩ -, and catecholamine-dependent aggregation properties (18).

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Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

Gallo

Levi²,

Ramella³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The major VSinduced actions consist of both negative inotropism (eel, frog, rat) and lusitropism (rat) and of the relevant counteraction of the bARs-mediated positive inotropism, typically induced by ISO (eel, frog, rat), achieved through a functional non-competitive type of antagonism (Fig. 5) Imbrogno et al, 2004;Cerra et al, 2006;Pieroni et al, 2007). As detailed in the rat heart, these effects are independent of f H and coronary performance and are comparable to those documented in the trabeculate and luminally supplied eel and frog hearts.…”

Section: Qkkhsgfedelsevlenqssqaelkeaveepsskdvmekrmentioning

confidence: 99%

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Tota

Cerra

Gattuso

2010

Journal of Experimental Biology

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Summary In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in ‘zero steady-state error’ homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize ‘whip-brake’ connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used as an intellectual tool to disentangle the experimental complexity of the mammalian and human endocrine hearts, suggesting future investigational avenues.

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Overexpression of vasostatin‐1 protects hypoxia/reoxygenation injuries in cardiomyocytes–endothelial cells transwell co‐culture system

Liu

Yang

Shi

et al. 2013

Cell Biology International

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Vasostatin-1 (VS-1) plays important roles in myocardial ischemia/reperfusion injury. We have explored the protective effects of VS-1 on cardiomyocytes using cardiomyocyte-endothelial cells Transwell Co-culture System. Cardiomyocytes and rat aortic endothelial cells (RAECs) were prepared from ventricles and thoraco-abdominal aorta of Sprague-Dawley rats. The experiment used cardiomyocytes alone culture group (C) and cardiomyocytes-RAECs co-culture group (T), each with three subgroups: C-Ad-Null, C-Ad-VS-1, C-Hb (Ad-VS-1 + NO scavenger Hb), or T-Ad-Null, T-Ad-VS-1 transfection, T-Hb. After 48 h incubation, all groups were treated with hypoxia for 60 min and then reoxygenated for 120 min. We also investigated endothelial cells-mediated cardiomyocytes protection. RAECs were treated with hypoxia for 30 min and reoxygenated with normal cardiomyocytes for 120 min. The cardiomyocytes apoptosis rate, aspartate aminotransferase (AST) and creatine kinase isozyme MB (CK-MB) were recorded. As expected, cardiomyocytes apoptosis, AST and CK-MB were significantly increased in the T-Ad-Null group than in the C-Ad-Null group. VS transfection significantly reduced these levels. However, apoptosis, AST and CK-MB levels were increased again after Hb treatment, returning to the similar level of the C-Ad-null group in the C-Hb group, but still significantly lower in the T-Hb group compared with the T-Ad-null group. RAEC injury caused cardiomyocyte injury, and VS-1 transfection of the RAEC decreased apoptosis and the levels of AST and CK-MB. The findings suggest that VS-1 exerts protective effects on the cardiomyocytes directly or indirectly by cardiomyocyte-endothelial cells interaction.

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Recombinant N–terminal fragments of chromogranin–A modulate cardiac function of the Langendorff–perfused rat heart

Cited by 70 publications

References 31 publications

Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Overexpression of vasostatin‐1 protects hypoxia/reoxygenation injuries in cardiomyocytes–endothelial cells transwell co‐culture system

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