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Thromb Haemost 2018; 118(01): 182-194
DOI: 10.1160/TH17-05-0349
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury–Induced Neointimal Hyperplasia

Miho Kojima   *
,
Nana Ozawa   *
,
Yusaku Mori
,
Yui Takahashi
,
Kaho Watanabe-Kominato
,
Remina Shirai
,
Rena Watanabe
,
Kengo Sato
,
Taka-aki Matsuyama
,
Hatsue Ishibashi-Ueda
,
Shinji Koba
,
Youichi Kobayashi
,
Tsutomu Hirano
,
Takuya Watanabe
Further Information

Publication History

22 May 2017

17 September 2017

Publication Date:
05 January 2018 (online)

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Abstract

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E–deficient (ApoE−/−) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE−/− mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury–induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.

Keywords

catestatin - atherosclerosis - restenosis - macrophage - smooth muscle

Financial Support

This work was supported in part by Grants-in-Aid for Scientific Research (C) (26460659 and 17K08993 to T.W.) from the Japan Society for the Promotion of Science.


* Miho Kojima and Nana Ozawa contributed equally to this work.


Supplementary Material

 

  • References

  • 1 Malyar NM, Reinecke H, Freisinger E. Restenosis after endovascular revascularization in peripheral artery disease. Vasa 2015; 44 (04) 257-270
    CrossrefPubMedGoogle Scholar
  • 2 Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006; 6 (07) 508-519
    CrossrefPubMedGoogle Scholar
  • 3 Yu XH, Fu YC, Zhang DW, Yin K, Tang CK. Foam cells in atherosclerosis. Clin Chim Acta 2013; 424: 245-252
    CrossrefPubMedGoogle Scholar
  • 4 De Paoli F, Staels B, Chinetti-Gbaguidi G. Macrophage phenotypes and their modulation in atherosclerosis. Circ J 2014; 78 (08) 1775-1781
    CrossrefPubMedGoogle Scholar
  • 5 Chistiakov DA, Sobenin IA, Orekhov AN. Vascular extracellular matrix in atherosclerosis. Cardiol Rev 2013; 21 (06) 270-288
    CrossrefPubMedGoogle Scholar
  • 6 Helle KB. The chromogranin A-derived peptides vasostatin-I and catestatin as regulatory peptides for cardiovascular functions. Cardiovasc Res 2010; 85 (01) 9-16
    CrossrefPubMedGoogle Scholar
  • 7 Helle KB, Corti A, Metz-Boutigue MH, Tota B. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 2007; 64 (22) 2863-2886
    CrossrefPubMedGoogle Scholar
  • 8 Krüger PG, Mahata SK, Helle KB. Catestatin (CgA344-364) stimulates rat mast cell release of histamine in a manner comparable to mastoparan and other cationic charged neuropeptides. Regul Pept 2003; 114 (01) 29-35
    CrossrefPubMedGoogle Scholar
  • 9 Pieroni M, Corti A, Tota B. , et al. Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function. Eur Heart J 2007; 28 (09) 1117-1127
    CrossrefPubMedGoogle Scholar
  • 10 Radek KA, Lopez-Garcia B, Hupe M. , et al. The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury. J Invest Dermatol 2008; 128 (06) 1525-1534
    CrossrefPubMedGoogle Scholar
  • 11 Mahapatra NR. Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure. Cardiovasc Res 2008; 80 (03) 330-338
    CrossrefPubMedGoogle Scholar
  • 12 Mahata SK, Kiranmayi M, Mahapatra NR. Catestain: a master regulator of cardiovascular functions. Curr Med Chem 2017 ; 24, In press
    PubMedGoogle Scholar
  • 13 Avolio E, Mahata SK, Mantuano E. , et al. Antihypertensive and neuroprotective effects of catestatin in spontaneously hypertensive rats: interaction with GABAergic transmission in amygdala and brainstem. Neuroscience 2014; 270: 48-57
    CrossrefPubMedGoogle Scholar
  • 14 Kennedy BP, Mahata SK, O'Connor DT, Ziegler MG. Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo. Peptides 1998; 19 (07) 1241-1248
    CrossrefPubMedGoogle Scholar
  • 15 Theurl M, Schgoer W, Albrecht K. , et al. The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. Circ Res 2010; 107 (11) 1326-1335
    CrossrefPubMedGoogle Scholar
  • 16 Penna C, Pasqua T, Amelio D. , et al. Catestatin increases the expression of anti-apoptotic and pro-angiogenetic factors in the post-ischemic hypertrophied heart of SHR. PLoS One 2014; 9 (08) e102536
    CrossrefPubMedGoogle Scholar
  • 17 Rabbi MF, Eissa N, Munyaka PM. , et al. Reactivation of intestinal inflammation is suppressed by catestatin in a murine model of colitis via M1 macrophages and not the gut microbiota. Front Immunol 2017; 8: 985
    CrossrefPubMedGoogle Scholar
  • 18 Liu R, Sun NL, Yang SN, Guo JQ. Catestatin could ameliorate proliferating changes of target organs in spontaneously hypertensive rats. Chin Med J (Engl) 2013; 126 (11) 2157-2162
    PubMedGoogle Scholar
  • 19 Brar BK, Helgeland E, Mahata SK. , et al. Human catestatin peptides differentially regulate infarct size in the ischemic-reperfused rat heart. Regul Pept 2010; 165 (01) 63-70
    CrossrefPubMedGoogle Scholar
  • 20 Penna C, Alloatti G, Gallo MP. , et al. Catestatin improves post-ischemic left ventricular function and decreases ischemia/reperfusion injury in heart. Cell Mol Neurobiol 2010; 30 (08) 1171-1179
    CrossrefPubMedGoogle Scholar
  • 21 Egger M, Beer AG, Theurl M. , et al. Monocyte migration: a novel effect and signaling pathways of catestatin. Eur J Pharmacol 2008; 598 (1-3): 104-111
    CrossrefPubMedGoogle Scholar
  • 22 Aung G, Niyonsaba F, Ushio H. , et al. Catestatin, a neuroendocrine antimicrobial peptide, induces human mast cell migration, degranulation and production of cytokines and chemokines. Immunology 2011; 132 (04) 527-539
    CrossrefPubMedGoogle Scholar
  • 23 Guo X, Zhou C, Sun N. The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca2+-calcineurin-NFAT signaling pathway. Biochem Biophys Res Commun 2011; 407 (04) 807-812
    CrossrefPubMedGoogle Scholar
  • 24 Choi Y, Miura M, Nakata Y. , et al. A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population. Endocr J 2015; 62 (09) 797-804
    CrossrefPubMedGoogle Scholar
  • 25 Liu L, Ding W, Zhao F, Shi L, Pang Y, Tang C. Plasma levels and potential roles of catestatin in patients with coronary heart disease. Scand Cardiovasc J 2013; 47 (04) 217-224
    CrossrefPubMedGoogle Scholar
  • 26 Meng L, Wang J, Ding WH. , et al. Plasma catestatin level in patients with acute myocardial infarction and its correlation with ventricular remodelling. Postgrad Med J 2013; 89 (1050): 193-196
    CrossrefPubMedGoogle Scholar
  • 27 Xu W, Yu H, Li W, Gao W, Guo L, Wang G. Plasma catestatin: a useful biomarker for coronary collateral development with chronic myocardial ischemia. PLoS One 2016; 11 (06) e0149062
    CrossrefPubMedGoogle Scholar
  • 28 Xu W, Yu H, Wu H, Li S, Chen B, Gao W. Plasma catestatin in patients with acute coronary syndrome. Cardiology 2017; 136 (03) 164-169
    CrossrefPubMedGoogle Scholar
  • 29 Zhu D, Xie H, Wang X, Liang Y, Yu H, Gao W. Correlation of plasma catestatin level and the prognosis of patients with acute myocardial infarction. PLoS One 2015; 10 (04) e0122993
    CrossrefPubMedGoogle Scholar
  • 30 Watanabe K, Watanabe R, Konii H. , et al. Counteractive effects of omentin-1 against atherogenesis. Cardiovasc Res 2016; 110 (01) 118-128
    CrossrefPubMedGoogle Scholar
  • 31 Watanabe R, Watanabe H, Takahashi Y. , et al. Atheroprotective effects of tumor necrosis factor-stimulated gene-6. JACC Basic Transl Sci 2016; 1 (06) 494-509
    PubMedGoogle Scholar
  • 32 Sato K, Shirai R, Hontani M. , et al. Potent vasoconstrictor kisspeptin-10 induces atherosclerotic plaque progression and instability: reversal by its receptor GPR54 antagonist. J Am Heart Assoc 2017; 6 (04) e005790
    CrossrefPubMedGoogle Scholar
  • 33 Hasegawa A, Sato K, Shirai R. , et al. Vasoprotective effects of urocortin 1 against atherosclerosis in vitro and in vivo. PLoS One 2014; 9 (12) e110866
    CrossrefPubMedGoogle Scholar
  • 34 Naito C, Hashimoto M, Watanabe K. , et al. Facilitatory effects of fetuin-A on atherosclerosis. Atherosclerosis 2016; 246: 344-351
    CrossrefPubMedGoogle Scholar
  • 35 Konii H, Sato K, Kikuchi S. , et al. Stimulatory effects of cardiotrophin 1 on atherosclerosis. Hypertension 2013; 62 (05) 942-950
    CrossrefPubMedGoogle Scholar
  • 36 Bandyopadhyay GK, Vu CU, Gentile S. , et al. 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 2012; 287 (27) 23141-23151
    CrossrefPubMedGoogle Scholar
  • 37 Sata M, Maejima Y, Adachi F. , et al. A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia. J Mol Cell Cardiol 2000; 32 (11) 2097-2104
    CrossrefPubMedGoogle Scholar
  • 38 Tangirala RK, Rubin EM, Palinski W. Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice. J Lipid Res 1995; 36 (11) 2320-2328
    PubMedGoogle Scholar
  • 39 Suo J, Ferrara DE, Sorescu D, Guldberg RE, Taylor WR, Giddens DP. Hemodynamic shear stresses in mouse aortas: implications for atherogenesis. Arterioscler Thromb Vasc Biol 2007; 27 (02) 346-351
    PubMedGoogle Scholar
  • 40 Imanaka-Yoshida K, Matsuura R, Isaka N, Nakano T, Sakakura T, Yoshida T. Serial extracellular matrix changes in neointimal lesions of human coronary artery after percutaneous transluminal coronary angioplasty: clinical significance of early tenascin-C expression. Virchows Arch 2001; 439 (02) 185-190
    CrossrefPubMedGoogle Scholar
  • 41 Holt AW, Tulis DA. Experimental rat and mouse carotid artery surgery: injury & remodeling studies. ISRN Minim Invasive Surg 2013; 2013: 167407
    PubMedGoogle Scholar
  • 42 Wang X, Xu S, Liang Y. , et al. Dramatic changes in catestatin are associated with hemodynamics in acute myocardial infarction. Biomarkers 2011; 16 (04) 372-377
    CrossrefPubMedGoogle Scholar
  • 43 Meng L, Ye XJ, Ding WH. , et al. Plasma catecholamine release-inhibitory peptide catestatin in patients with essential hypertension. J Cardiovasc Med (Hagerstown) 2011; 12 (09) 643-647
    CrossrefPubMedGoogle Scholar
  • 44 Liu L, Ding W, Li R. , et al. Plasma levels and diagnostic value of catestatin in patients with heart failure. Peptides 2013; 46: 20-25
    CrossrefPubMedGoogle Scholar
  • 45 Bassino E, Fornero S, Gallo MP. , et al. Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential. PLoS One 2015; 10 (03) e0119790
    CrossrefPubMedGoogle Scholar
  • 46 Liao F, Zheng Y, Cai J. , et al. Catestatin attenuates endoplasmic reticulum induced cell apoptosis by activation type 2 muscarinic acetylcholine receptor in cardiac ischemia/reperfusion. Sci Rep 2015; 5: 16590
    CrossrefPubMedGoogle Scholar
  • 47 Perrelli MG, Tullio F, Angotti C. , et al. Catestatin reduces myocardial ischaemia/reperfusion injury: involvement of PI3K/Akt, PKCs, mitochondrial KATP channels and ROS signalling. Pflugers Arch 2013; 465 (07) 1031-1040
    CrossrefPubMedGoogle Scholar
  • 48 Loppnow H, Libby P. Adult human vascular endothelial cells express the IL6 gene differentially in response to LPS or IL1. Cell Immunol 1989; 122 (02) 493-503
    CrossrefPubMedGoogle Scholar
  • 49 Holst JJ, Ehrhart-Bornstein M, Messell T, Poulsen SS, Harling H. Release of galanin from isolated perfused porcine adrenal glands: role of splanchnic nerves. Am J Physiol 1991; 261 (1, Pt 1): E31-E40
    PubMedGoogle Scholar