The adipokine apelin-13 induces expression of prothrombotic tissue factor

Plinio Cirillo; Francesca Ziviello; Grazia Pellegrino; Stefano Conte; Giovanni Cimmino; Alessandro Giaquinto; Francesco Pacifico; Antonio Leonardi; Paolo Golino; Bruno Trimarco

doi:10.1160/TH14-05-0451

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 113(02): 363-372
DOI: 10.1160/TH14-05-0451

Cellular Signalling and Proteolysis

Schattauer GmbH

The adipokine apelin-13 induces expression of prothrombotic tissue factor

Plinio Cirillo

¹Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, “Federico II”, Naples, Italy

,

Francesca Ziviello

¹Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, “Federico II”, Naples, Italy

,

Grazia Pellegrino

²Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy

,

Stefano Conte

²Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy

,

Giovanni Cimmino

²Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy

,

Alessandro Giaquinto

¹Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, “Federico II”, Naples, Italy

,

Francesco Pacifico

³Department of Molecular Medicine and Medical Biotechnology, University of Naples, “Federico II”, Naples, Italy

,

Antonio Leonardi

³Department of Molecular Medicine and Medical Biotechnology, University of Naples, “Federico II”, Naples, Italy

,

Paolo Golino

²Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy

,

Bruno Trimarco

¹Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, “Federico II”, Naples, Italy

› Institutsangaben

Abstract

Summary

Adipocytes are cells able to produce and secrete several active substances (adipokines) with direct effects on vascular cells. Apelin, one of the most recently identified adipokines has been studied in cardiovascular system physiology in regard to vessel vasodilation and myocardial contraction, but it has not yet completely characterised for its pathophysiological role in cardiovascular disease and especially in acute coronary syndromes (ACS). Several studies have indicated that tissue factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of apelin 12 and apelin 13 on TF in human umbilical endothelial cells (HUVECs) and monocytes. Cells were stimulated with increasing concentrations of apelin 12 or apelin 13 and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and pro-coagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that apelin 13 but not apelin 12 induces transcription of mRNA for TF. In addition, we show that this adipokine promotes surface expression of TF that is functionally active. Apelin 13 effects on TF appear modulated by the activation of the G-protein-transcription factor nuclear factor (NF)-ΚB axis since G-protein inhibitors suppressed NF-ΚB mediated TF expression. Data of the present study, although in vitro, indicate that apelin-13, induces a procoagulant phenotype in HUVECs and monocytes by promoting TF expression. These observations support the hypothesis that this adipokine might play a relevant role as an active partaker in athero-thrombotic disease.

Keywords

Adipokines - atherothrombosis - tissue factor

Volltext

Referenzen

References
1 Hubert HB. et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67: 968-977.
2 Berg AH, Scherer PE. Adipose Tissue, Inflammation, and Cardiovascular Disease. Circ Res 2005; 96: 939-994.
3 Sowers JR. Obesity as a cardiovascular risk factor. Am J Med 2003; 115: 37-41.
4 Maresca F. et al. Adipokines, Vascular Wall, and Cardiovascular Disease: A Focused Overview of the Role of Adipokines in the Pathophysiology of Cardiovascular Disease. Angiol. 2014 Epub ahead of print.
5 Tatemoto K. et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251: 471-476.
6 Masri B. et al. Apelin signalling: a promising pathway from cloning to pharmacology. Cell Signal 2005; 17: 415-426.
7 El Messari S. et al. Functional dissociation of apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure. J Neurochem 2004; 90: 1290-1301.
8 Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005; 107: 198-211.
9 Malyszko J. et al. Visfatin and apelin, new adipokines, and their relation to endothelial function in patients with chronic heart failure. Adv Med Sci 2008; 53: 32-36.
10 Farkasfalvi K. et al. Direct effects of apelin on cardiomycocite contractility and electrophysiology. Biochem Biophys Res Commun 2007; 357: 889-895.
11 Lu Y. et al. Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF.kB/JNK signal pathway in human umbilical vein endothelial cells. Amino Acids 2012; 43: 2125-2136.
12 Libby P. et al. Inflammation and atherosclerosis. Circulation 2002; 105: 1135-1143.
13 Ross R. The pathogenesis of atherosclerosis-an update. N Engl J Med 1986; 314: 488-500.
14 Annex BH. et al. Differential expression of tissue factor protein in directional atherectomy specimens from patients with stable and unstable coronary syndromes. Circulation 1995; 91: 619-622.
15 Pawashe AB. et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res 1994; 74: 56-63.
16 Ragni M. et al. Monoclonal antibody against tissue factor shortens tissue plasminogen activator lysis time and prevents reocclusion in a rabbit model of carotid artery thrombosis. Circulation 1996; 93: 1913-1918.
17 Wilcox JN. et al. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-2843.
18 Chen J. et al. Tissue factor – a receptor involved in the control of cellular properties including angiogenesis. Thromb Haemost 2001; 86: 334-345.
19 Rao LV, Pendurthi UR. Tissue factor on cells. Blood Coagul Fibrinolysis 1998; 09: 27-35.
20 Cirillo P. et al. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res 2005; 68: 47-55.
21 Masri B. et al. Apelin activates extracellular signal regulated kinases via a PTX-sensitive G protein. Biochem Biophys Res Commun 2002; 90: 539-545.
22 Cirillo P. et al. Pro Athero-thrombotic Effects of Leptin in Human Coronary Endothelial Cells. Thromb Haemost 2010; 103: 1065-1075.
23 Cirillo P. et al. The adipokine visfatin induces Tissue Factor expression in human coronary artery endothelial cells. Another piece in the adipokines puzzle. Thromb Res 2012; 130: 403-408.
24 Eckel RH, Krauss RM. American Heart Association call to action: obesity as a major risk factor for coronary artery disease. AHA nutrition committee. Circulation 1998; 97: 2099-2100.
25 Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab 2000; 11: 327-332.
26 Calabrò P. et al. Tissue Factor is Induced by Resistin in Human Coronary Artery Endothelial Cells by NF-kB-dependent Pathway. J Vasc Res 2011; 48: 59-66.
27 Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005; 107: 198-211.
28 Liu XY. et al. Apelin-13 increases expression of ATP-binding cassette transported A1 via activating protein kinase C alpha signaling in THP-1 macrophage-derived foam cells. Atherosclerosis 2013; 226: 398-407.
29 Weir RAP. et al. Plasma apelin concentration is depressed following acute myocardial infarction in man. Eur J Heart Fail 2009; 11: 551-558.
30 Kadoglou NPE. et al. Serum levels of apelin and gherlin in patients with acute coronary syndromes and established coronary artery disease-KOZANI STUDY. Transl Res 2010; 155: 238-246.
31 Pitkin Sl. et al. Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br J Pharmacol 2010; 160: 1785-1795.
32 Kojima Y. et al. Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse. Cardiovasc Res 2010; 87: 156-165.
33 Li F. et al. Apelin-induced vascular smooth muscle cell proliferation: the regulation of cyclin D. Front Biosci 2008; 13: 3786-3792.
34 Hosoya M. et al. Molecular and functional characteristics of APJ: tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 2000; 275: 21061-21067.
35 Fan X. et al. Structural and functional study of the apelin 13 peptide, an endogenous ligand of HIV-1 coreceptor. APJ Biochemistry 2003; 42: 10163-10168.
36 Lee DK. et al. The fate of internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with beta-arrestin. Biochem Biophys Res Commun 2010; 395: 185-189.
37 Pisarenko OI. et al. In vivo reduction of reperfusion injuty to the heart with apelin-12 peptide in rats. Bull Exp Biol Med 2011; 152: 79-82.
38 Golino P. et al. Recombinant human, active site-blocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits. Am J Physiol Heart Circ Physiol 2000; 278: H1507-1516.
39 Barnes PJ, Karin M. Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory disease. N Engl J Med 1997; 336: 1066-1071.
40 Oeth P. et al. RegulatMackman Ne tissue factor gene in human monocytic cells. Arteriocler Thromb Vasc Biol 1997; 17: 365-374.
41 Ritchie ME. Nuclear Factor- kB is selectively and markedly activated in humans with unstable angina pectoris. Circulation 1998; 98: 1707-1713.
42 Wilson SH. et al. Nuclear factor-kappaB immunoreactivity is present in human coronary plaque and enhanced in patients with unstable angina pectoris. Atherosclerosis 2002; 160: 147-153.
43 Zhen EY. et al. Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma. Anal Biochem 2013; 442: 1-9.