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Cardiac Physio-Pharmacological Aspects of Three Chromogranin A-Derived Peptides: Vasostatin, Catestatin, and Serpinin

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Chromogranins: from Cell Biology to Physiology and Biomedicine

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Abstract

The discovery of a cardiac production of Chromogranin A (CgA) opened a rich field of research whose result was a cardiovascular dimension of this multifunctional protein and the fragments derived by its proteolytic cleavage. In line with its precursor function, at the cardiac level, CgA undergoes proteolytic processing. Moreover, as shown by ex vivo functional studies, it acts on the heart itself. Through the amino terminal (vasostatin: VS) and catestatin (CST) domains, CgA elicits a direct cardiodepressive, antiadrenergic and cardioprotective influence, acting as a cardiac stabilizer under normal conditions and in the presence of stress (i.e. catecholaminergic, and endothelinergic). At the same time, through the C-terminal Serpinin (Serp), CgA elicits a cardiostimulatory beta-adrenergic-like action. In this chapter, the results of more than 10 years of research will be described in order to illustrate the cardiovascular profile of these peptides, as well as their mechanisms of action. The purpose is to highlight the expanding role this protein and its fragments in the neuroendocrine circuits that finely control heart performance in health and disease.

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Abbreviations

AD:

Adenylate Cyclase

Akt:

Protein Kinase B

Au:

Aurum

CA:

Catecholamine

CaM:

Calmodulin

cAMP:

Cyclic Adenosine Monophosphate

CgA:

Chromogranin A

cGMP:

Cyclic Guanosine Monophosphate

Chr:

Chromofungin

CO:

Cardiac Output

CP:

Coronary Pressure

CST:

Catestatin

ECM:

Myocardial Extracellular Matrix

EE:

Endocardial endothelium

ELISA:

Enzyme-Linked Immuno Assay

eNOS:

Endothelial Nitric Oxide Synthase

ERK1/2:

Extracellular Signal–regulated Kinase 1/2

ET-1:

Endothelin 1

GC:

Guanylate Cyclase

GPCR:

G protein-coupled receptor

GSK3β:

Glycogen Synthase Kinase 3 beta

HF:

Heart Failure

HPLC:

High-performance liquid chromatography

HR:

Heart rate

hr:

human recombinant

Hsp90:

Heat Shock Protein 90

HTR:

Half Time Relaxation

I/R:

Ischemia/Reperfusion

IGF-1:

insulin-like growth factor-1

iPLA2:

Calcium Independent Phospholipase A2

IS:

Infarct Size

ISO:

Isoproterenol

LDH:

Lactate Dehydrogenase

L-NAME:

Nω-Nitro-L-arginine methyl ester hydrochloride

LVP:

Left Ventricular Pressure

miRNA:

microRNA

mitoKATP Channel:

ATP-Sensitive Potassium Channel

nAChR:

Nicotinic Receptor

NO:

Nitric Oxide

ODQ:

1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one

PDE2:

Phosphodiesterases type 2

pGlu-Serp:

pyroglutaminated-Serpinin

PI3K:

Phosphatidylinositide 3-Kinase

PKA:

Protein Kinase A

PKG:

Protein Kinase G

PLN:

Phospholamban

PTIO:

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide

PTX:

Pertussis Toxin

RISK:

Reperfusion Injury Signalling Kinase

ROS:

Radical Oxygen Species

RPP:

Rate Pressure Product

RyR:

Ryanodine receptor

Serp:

Serpinin

SHR:

Spontaneously Hypertensive Rats

SR:

Sarcoplasmic Reticulum

VE:

Vascular Endothelium

VS:

Vasostatin

WKY:

Wistar Kyoto

WT:

Wild-Type

β-ARs:

β-adrenergic receptors

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Authors and Affiliations

  1. Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036, Arcavacata di Rende (CS), Italy

    Tommaso Angelone PhD, Bruno Tota & Maria Carmela Cerra

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  1. Tommaso Angelone PhD
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  2. Bruno Tota
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  3. Maria Carmela Cerra
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Correspondence to Tommaso Angelone PhD .

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Editors and Affiliations

  1. Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy

    Tommaso Angelone

  2. Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy

    Maria Carmela Cerra

  3. Department of Biology, Ecology and Earth Science, University of Calabria, Arcavacata di Rende, Cosenza, Italy

    Bruno Tota

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Angelone, T., Tota, B., Cerra, M.C. (2017). Cardiac Physio-Pharmacological Aspects of Three Chromogranin A-Derived Peptides: Vasostatin, Catestatin, and Serpinin. In: Angelone, T., Cerra, M., Tota, B. (eds) Chromogranins: from Cell Biology to Physiology and Biomedicine. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-319-58338-9_8

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