Horm Metab Res 2006; 38(11): 767-772
DOI: 10.1055/s-2006-955090
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Increased Prolactin in Acute Coronary Syndromes as Putative Co-activator of ADP-stimulated P-Selectin Expression

D. Raaz 1 , H. Wallaschofski 2 , C. Stumpf 1 , A. Yilmaz 1 , I. Cicha 1 , L. Klinghammer 1 , W. G. Daniel 1 , T. Lohmann 3 , C. D. Garlichs 1
  • 1Medical Clinic 2, University Hospital Erlangen, Germany
  • 2Medical Clinic A, University Clinic of Greifswald, Germany
  • 3City Hospital Dresden-Neustadt, Germany
Weitere Informationen

Publikationsverlauf

Received 23 February 2006

Accepted after revision 28 August 2006

Publikationsdatum:
16. November 2006 (online)

Abstract

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r2=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.

References

  • 1 Golino P, Ravera A, Ragni M, Cirillo P, Piro O, Chiariello M. Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes.  Circulation. 2003;  108 2864-2869
  • 2 Hamsten A, Eriksson P, Karpe F, Silveira A. Relationships of thrombosis and fibrinolysis to atherosclerosis.  Curr Opin Lipidol. 1994;  5 382-389
  • 3 Gaustadnes M, Rudiger N, Moller J, Rasmussen K, Bjerregaard Larsen T, Ingerslev J. Thrombophilic predisposition in stroke and venous thromboembolism in Danish patients.  Blood Coagul Fibrinolysis. 1999;  10 251-259
  • 4 Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis.  Circulation. 2002;  105 1135-1143
  • 5 Ruggeri ZM. Platelets in atherothrombosis.  Nat Med. 2002;  8 1227-1234
  • 6 Merten M, Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates.  Circulation. 2000;  102 1931-1936
  • 7 Xu DY, Zhao SP, Peng WP. Elevated plasma levels of soluble P-selectin in patients with acute myocardial infarction and unstable angina. An inverse link to lipoprotein(a).  Int J Cardiol. 1998;  64 253-258
  • 8 Garlichs CD, Eskafi S, Raaz D, Schmidt A, Ludwig J, Herrmann M, Klinghammer L, Daniel WG, Schmeisser A. Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets.  Heart. 2001;  86 649-655
  • 9 Aukrust P, Muller F, Ueland T, Berget T, Aaser E, Brunsvig A, Solum NO, Forfang K, Froland SS, Gullestad L. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina: possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes.  Circulation. 1999;  100 614-620
  • 10 Wallaschofski H, Donne M, Eigenthaler M, Hentschel B, Faber R, Stepan H, Koksch M, Lohmann T. PRL as a novel potent cofactor for platelet aggregation.  J Clin Endocrinol Metab. 2001;  86 5912-5919
  • 11 Wallaschofski H, Kobsar A, Koksch M, Siegemund A, Hentschel B, Tuschy U, Lohmann T, Sokolova O, Eigenthaler M. Prolactin receptor signaling during platelet activation.  Horm Metab Res. 2003;  35 228-235
  • 12 Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotes aggregation of human platelets via the long form of its receptor.  Diabetes. 1999;  48 426-429
  • 13 Maruyama I, Nakata M, Yamaji K. Effect of leptin in platelet and endothelial cells. Obesity and arterial thrombosis.  Ann N Y Acad Sci. 2000;  902 315-319
  • 14 Konstantinides S, Schafer K, Loskutoff DJ. The prothrombotic effects of leptin possible implications for the risk of cardiovascular disease in obesity.  Ann N Y Acad Sci. 2001;  947 134-141
  • 15 Meisel SR, Ellis M, Pariente C, Pauzner H, Liebowitz D, David D, Shimon I. Serum leptin levels increase following acute myocardial infarction.  Cardiology. 2001;  95 206-211
  • 16 Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, Olsson T. Leptin is associated with increased risk of myocardial infarction.  J Intern Med. 1999;  246 409-418
  • 17 La Follette L, Gordon EM, Mazur CA, Ratnoff OD, Yamashita TS. Hyperprolactinemia and reduction in plasma titers of Hageman factor, prekallikrein, and high molecular weight kininogen in patients with acute myocardial infarction.  J Lab Clin Med. 1987;  110 318-321
  • 18 Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice.  Endocr Rev. 1998;  19 225-268
  • 19 Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.  Nature. 1998;  394 897-901
  • 20 Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR. Biological action of leptin as an angiogenic factor.  Science. 1998;  281 1683-1686
  • 21 Bonomo T, Lisboa PC, Passos MCF, Pazos-Moura CC, Reis AM, Moura EG. Prolactin inhibition in lactating rats changes leptin transfer through the milk.  Horm Metab Res. 2005;  37 220-225
  • 22 Wallaschofski H, Kobsar A, Sokolova O, Eigenthaler M, Lohmann T. Co-activation of platelets by prolactin or leptin-pathophysiological findings and clinical implications.  Horm Metab Res. 2004;  36 1-6
  • 23 Wallaschofski H, Kobsar A, Sokolova O, Siegemund A, Stepan H, Faber R, Eigenthaler M, Lohmann T. Differences in platelet activation by prolactin and leptin.  Horm Metab Res. 2004;  36 453-457
  • 24 Merten M, Chow T, Hellums JD, Thiagarajan P. A new role for P-selectin in shear-induced platelet aggregation.  Circulation. 2000;  102 2045-2050
  • 25 Lehr HA, Olofsson AM, Carew TE, Vajkoczy P, von Adrian UH, Hubner C, Berndt MC, Steinberg D, Messmer K, Arfors KE. P-selectin mediates the interaction of circulating leukocytes with platelets and microvascular endothelium in response to oxidized lipoprotein in vivo.  Lab Invest. 1994;  71 380-386
  • 26 Gauthior TW, Scalia R, Murohara T, Guo JP, Lefer AM. Nitric oxide protects against leukocyte-endothelium interactions in the early states of hypercholesterolemia.  Arterioscler Thromb Vasc Biol. 1995;  15 1652-1659
  • 27 Ikeda H, Takajo Y, Ichiki K, Ueno T, Maki S, Noda T, Sugi K, Imaizumi T. Increased soluble form of P-selectin in patients with unstable angina.  Circualtion. 1995;  92 1693-1696
  • 28 Pepys MB, Hirschfield GM. C-reactive protein: a critical update.  J Clin Invest. 2003;  111 1805-1812
  • 29 Lind L. Circulating markers of inflammation and atherosclerosis.  Atherosclerosis. 2003;  169 203-214
  • 30 Ridker PM, Haughie P. Prospective studies of C-reactive protein as a risk factor for cardiovascular disease.  J Investig Med. 1998;  46 391-395
  • 31 Blann AD, Nadar SK, Lip GY. The adhesion molecule P-selectin and cardiovascular disease.  Eur Heart J. 2003;  24 2166-2179
  • 32 Woodman RJ, Watts GF, Puddey IB, Burke V, Mori TA, Hodgson JM, Beilin LJ. Leukocyte count and vascular function in Type 2 diabetic subjects with treated hypertension.  Atherosclerosis. 2002;  163 175-181
  • 33 Garlichs CD, John S, Schmeisser A, Eskafi S, Stumpf C, Karl M, Goppelt-Struebe M, Schmieder R, Daniel WG. Upregulation of CD40 and CD40 Ligand (CD154) in patients with moderate hypercholesterolemia.  Circulation. 2001;  104 2395-2400
  • 34 Stubbs PJ, Laycock J, Alaghband-Zadeh J, Carter G, Noble MI. Circulating stress hormone and insulin concentrations in acute coronary syndromes: identification of insulin resistance on admission.  Clin Sci. 1999;  96 589-595
  • 35 Morales T, Sawchenko PE. Brainstem prolactin-releasing peptide neurons are sensitive to stress and lactation.  Neuroscience. 2003;  121 771-778
  • 36 Clevenger CV, Freier DO, Kline JB. Prolactin receptor signal transduction in cells of the immune system.  J Endocrinol. 1998;  157 187-197
  • 37 Freeman MF, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion.  Physiol Rev. 2000;  80 1523-1631
  • 38 Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzman M, Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty oxidation via protein kinase.  A J Biol Chem. 2001;  276 25096-25100

1 DR and HW have contributed equally to this work.

Correspondence

Dr. Dorette Raaz

Department of Cardiology·Medical Clinic 2·University Hospital Erlangen

Ulmenweg 18

91054 Erlangen

Germany

Telefon: +49/9131/85 35 30 1

Fax: +49/9131/85 35 30 3

eMail: dorette.raaz@med2.imed.uni-erlangen.de