Abstract
Catestatin (CST) was first named in 1997 for its catecholamine-inhibitory activity. It was discovered as a potent inhibitor of catecholamine secretion and as a regulator of histamine release. Accumulating evidence shows that CST is involved with cardiovascular diseases; however, whether CST is a protective factor for these conditions and the mechanisms by which such actions may be mediated are not well understood. In this article, we review recent basic research and clinical trials in the study of CST and summarize the association of CST with cardiovascular diseases. We review data obtained from MedLine via PubMed and from our own investigations.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 . Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature 215(5096), 58–59 (1967).
- 2 . Secretion from the adrenal medulla: biochemical evidence for exocytosis. Br. J. Pharmacol. Chemother. 31(1), 94–104 (1967).
- 3 . Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324(6096), 476–478 (1986).
- 4 Inhibition of insulin secretion by betagranin, an N-terminal chromogranin A fragment. J. Biol. Chem. 282(17), 12717–12724 (2007).
- 5 . The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. Regul. Pept. 41(1), 9–18 (1992).
- 6 . Parastatin (porcine chromogranin A347–419), a novel chromogranin A-derived peptide, inhibits parathyroid cell secretion. Endocrinology 133(2), 461–466 (1993).
- 7 . Secretion from chromaffin cells is controlled by chromogranin A-derived peptides. Proc. Natl Acad. Sci USA 85, 1712–1716 (1988). • This was the first paper that predicted the exitence of CST.
- 8 Novel autocrine feedback control of catecholamine release. A discrete chromogranin A fragment is a noncompetitive nicotinic cholinergic antagonist. J. Clin. Invest. 100(6), 1623–1633 (1997). • This is the first paper that identified CST and its basic function to inhibit catecholamine release.
- 9 . Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299(6), 6 (2010).
- 10 Catestatin (chromogranin A(352–372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling. J. Biol. Chem. 287(27), 23141–23151 (2012).
- 11 A neuroendocrine antimicrobial peptide, catestatin, stimulates interleukin-8 production from human keratinocytes via activation of mitogen-activated protein kinases. J. Dermatol. Sci. 61(2), 142–144 (2010).
- 12 Catestatin, an endogenous chromogranin A-derived peptide, inhibits in vitro growth of Plasmodium falciparum. Cell. Mol. Life Sci. 67(6), 1005–1015 (2010).
- 13 The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury. J. Invest. Dermatol. 128(6), 1525–1534 (2008).
- 14 Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2. PLoS ONE 4(2), 19 (2009).
- 15 Monocyte migration: a novel effect and signaling pathways of catestatin. Eur. J. Pharmacol. 598(1–3), 104–111 (2008).
- 16 . The catecholamine release-inhibitory peptide catestatin (chromogranin A344–363) modulates myocardial function in fish. J. Exp. Biol. 213(Pt 21), 3636–3643 (2010).
- 17 . Mast cell chemotaxis – chemoattractants and signaling pathways. Front. Immunol. 3, 119 (2012).
- 18 . Early decline in the catecholamine release-inhibitory peptide catestatin in humans at genetic risk of hypertension. J. Hypertens. 20(7), 1335–1345 (2002).
- 19 Plasma catecholamine release-inhibitory peptide catestatin in patients with essential hypertension. J. Cardiovasc. Med. 12(9), 643–647 (2011).
- 20 Chromogranin A polymorphisms are associated with hypertensive renal disease. J. Am. Soc. Nephrol. 19(3), 600–614 (2008).
- 21 . Catestatin is useful in detecting patients with stage B heart failure. Biomarkers 16(8), 691–697 (2011).
- 22 Plasma levels and diagnostic value of catestatin in patients with heart failure. Peptides 46, 20–25 (2013).
- 23 Dramatic changes in catestatin are associated with hemodynamics in acute myocardial infarction. Biomarkers 16(4), 372–377 (2011).
- 24 Conformational preferences and activities of peptides from the catecholamine release-inhibitory (catestatin) region of chromogranin A. Regul. Pept. 118(1–2), 75–87 (2004).
- 25 . Novel peptide isomer strategy for stable inhibition of catecholamine release: application to hypertension. Hypertension 60(6), 1552–1559 (2012).
- 26 . Development of a pharmacophore model for the catecholamine release-inhibitory peptide catestatin: virtual screening and functional testing identify novel small molecule therapeutics of hypertension. Bioorg. Med. Chem. 21(18), 5855–5869 (2013).
- 27 Formation of the catecholamine release-inhibitory peptide catestatin from chromogranin A. Determination of proteolytic cleavage sites in hormone storage granules. J. Biol. Chem. 275(30), 22905–22915 (2000).
- 28 . Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a β-strand/loop/β-strand structure secured by hydrophobic interactions and predictive of activity. Regul. Pept. 77, 43–53 (1998).
- 29 . Chromogranin/secretogranin proteins in murine heart: myocardial production of chromogranin A fragment catestatin (Chga(364–384)). Cell Tissue Res. 342(3), 353–361 (2010).
- 30 Catestatin–a novel neuropeptide in carcinoid tumors of the appendix. Anticancer Res. 24(1), 311–316 (2004).
- 31 . Distribution of catestatin-like immunoreactivity in the human auditory system. Hearing Res. 184(1–2), 16–26 (2003).
- 32 New antimicrobial activity for the catecholamine release-inhibitory peptide from chromogranin A. Cell. Mol. Life Sci. 62(3), 377–385 (2005).
- 33 The catecholamine release-inhibitory “catestatin” fragment of chromogranin a: naturally occurring human variants with different potencies for multiple chromaffin cell nicotinic cholinergic responses. Mol. Pharmacol. 66(5), 1180–1191 (2004).
- 34 . The chromogranin A fragment catestatin: specificity, potency and mechanism to inhibit exocytotic secretion of multiple catecholamine storage vesicle co-transmitters. J. Hypertens. 24(5), 895–904 (2006).
- 35 . Desensitization of catecholamine release. The novel catecholamine release-inhibitory peptide catestatin (chromogranin a344–364) acts at the receptor to prevent nicotinic cholinergic tolerance. J. Biol. Chem. 274(5), 2920–2928 (1999).
- 36 . Interaction of the catecholamine release-inhibitory peptide catestatin (human chromogranin A(352–372)) with the chromaffin cell surface and Torpedo electroplax: implications for nicotinic cholinergic antagonism. Regul. Pept. 95(1–3), 9–17 (2000). • This is an important evidence that CST binds to nAchR receptor and inhibits catecholamine release.
- 37 Catecholamine secretory vesicle stimulus-transcription coupling in vivo. Demonstration by a novel transgenic promoter/photoprotein reporter and inhibition of secretion and transcription by the chromogranin A fragment catestatin. J. Biol. Chem. 278(34), 32058–32067 (2003).
- 38 Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor. J. Cell Sci. 125(2787), 2323–2337 (2012).
- 39 . Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo. Peptides 19(7), 1241–1248 (1998). • Showed CST inhibits histamine release.
- 40 . Catestatin (chromogranin A344–358) stimulates release of histamine from rat pleural and peritoneal mast cells. Ann. N. Y. Acad. Sci. 971, 349–351 (2002).
- 41 . Catestatin (CgA344–364) stimulates rat mast cell release of histamine in a manner comparable to mastoparan and other cationic charged neuropeptides. Regul. Pept. 114(1), 29–35 (2003).
- 42 Catestatin (chromogranin A344–364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart. Am. J. Physiol. Heart Circ. Physiol. 295(1), 9 (2008).
- 43 A novel catestatin-induced antiadrenergic mechanism triggered by the endothelial PI3K–eNOS pathway in the myocardium. Cardiovasc. Res. 91(4), 617–624 (2011). • Provides evidence that CST inhibit inotropism and lusitropism through PI3K-eNOS pathway.
- 44 Phosphodiesterase type-2 and NO-dependent S-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin. Am. J. Physiol. Heart Circ. Physiol. 302(2), 4 (2012).
- 45 . Cardiac heterometric response: the interplay between catestatin and nitric oxide deciphered by the frog heart. Nitric Oxide 27(1), 40–49 (2012).
- 46 Catecholamine release-inhibitory peptide catestatin (chromogranin A(352–372)): naturally occurring amino acid variant Gly364Ser causes profound changes in human autonomic activity and alters risk for hypertension. Circulation 115(17), 2271–2281 (2007).
- 47 Catestatin improves post-ischemic left ventricular function and decreases ischemia/reperfusion injury in heart. Cell. Mol. Neurobiol. 30(8), 1171–1179 (2010).
- 48 Catestatin reduces myocardial ischaemia/reperfusion injury: involvement of PI3K/Akt, PKCs, mitochondrial KATP channels and ROS signalling. Pflugers Arch. 465(7), 1031–1040 (2013).
- 49 Human catestatin peptides differentially regulate infarct size in the ischemic-reperfused rat heart. Regul. Pept. 165(1), 63–70 (2010).
- 50 The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. Circ. Res. 107(11), 1326–1335 (2010). • Offers mechanisms for CST causing angiogenesis.
- 51 Obligatory role for endothelial heparan sulphate proteoglycans and caveolae internalization in catestatin-dependent eNOS activation. BioMed. Res. Int. 2014, 783623 (2014).
- 52 . The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca2+-calcineurin-NFAT signaling pathway. Biochem. Biophys. Res. Commun. 407(4), 807–812 (2011).
- 53 . ACE2/Ang-(1–7) signaling and vascular remodeling. Sci. China Life Sci. 57(8), 802–808 (2014).
- 54 The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: Influence on high-density lipoprotein cholesterol. Anatol. J. Cardiol. 15(7), 577–585 (2015).
- 55 Plasma catestatin level in patients with acute myocardial infarction and its correlation with ventricular remodelling. Postgrad. Med. J. 89(1050), 193–196 (2013).
- 56 . Correlation of plasma catestatin level and the prognosis of patients with acute myocardial infarction. PLoS ONE 10(4), e0122993 (2015). • Follows up AMI patients and validated the correlation between plasma catestatin level and prognosis of AMI patients.
- 57 . Plasma levels and potential roles of catestatin in patients with coronary heart disease. Scand. Cardiovasc. J. 47(4), 217–224 (2013).
- 58 Usefulness of catestatin to predict malignant arrhythmia in patients with acute myocardial infarction. Peptides 55, 131–135 (2014).
- 59 . Prognostic value of circulating catestatin levels for in-hospital heart failure in patients with acute myocardial infarction. Chin. J. Cardiol. 40(11), 914–919 (2012).
- 60 . Catestatin could ameliorate proliferating changes of target organs in spontaneously hypertensive rats. Chin. Med. J. 126(11), 2157–2162 (2013).
- 61 Direct vasoactive effects of the chromogranin A (CHGA) peptide catestatin in humans in vivo. Clin. Exp. Hypertens. 32(5), 278–287 (2010).