Thromboxane Biosynthesis, Neutrophil and Coagulative Activation in Type IIa Hypercholesterolemia

Giovanni Davì; Antonina Ganci; Maurizio Averna; Carlo Giammarresi; Carlo Barbagallo; Isabella Catalano; Anna Calà; Alberto Notarbartolo

doi:10.1055/s-0038-1649871

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1995; 74(04): 1015-1019
DOI: 10.1055/s-0038-1649871

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

Thromboxane Biosynthesis, Neutrophil and Coagulative Activation in Type IIa Hypercholesterolemia

Autor*innen

Giovanni Davì

¹The Department of Internal Medicine, University of Chieti, Italy
Antonina Ganci

The Department of Internal Medicine, University of Palermo, Italy
Maurizio Averna

The Department of Internal Medicine, University of Palermo, Italy
Carlo Giammarresi

The Department of Internal Medicine, University of Palermo, Italy
Carlo Barbagallo

The Department of Internal Medicine, University of Palermo, Italy
Isabella Catalano

The Department of Internal Medicine, University of Palermo, Italy
Anna Calà

The Department of Internal Medicine, University of Palermo, Italy
Alberto Notarbartolo

The Department of Internal Medicine, University of Palermo, Italy

Abstract

als PDF herunterladen

Summary

Thromboxane (Tx) A₂ biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because blood clotting activation is an important component of the inflammatory response, involved in the initiation and progression of atherosclerotic plaques, we have investigated TxA₂ biosynthesis, neutrophil activation and thrombin generation in 24 patients with type IIa hypercholesterolemia.

Urinary 11-dehydro-TxB₂, was significantly higher (p =0.0001) in patients than in 24 sex- and age matched healthy subjects. Similarly, prothrombin fragment 1+2 (F₁₊₂), thrombin-antithrombin III complexes and plasma elastase were significantly higher in patients than incontrols. Urinary 11-dehydro-TxB₂ excretion was correlated with plasma elastase (r = 0.758; p =0.000I), and prothrombin fragment 1+2 (r = 0.804; p = 0.001). The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 2 months) significantly reduced cholesterol levels, urinary 11-dehydro-TxB₂ excretion, plasma elastase and plasma F_l+2 in 8 patients.

We conclude that type IIa hypercholesterolemia is associated with biochemical evidence of platelet, neutrophil and blood clotting activation. The relationship between these events remains to be investigated.

PDF (300 kb)

Referenzen

References
1 Ross R. The pathogenesis of atherosclerosis. In: Heart Disease. Braunwald E. ed. Philadelphia: Saunders; 1988: 1135-1152
2 Schrör K. Platelet reactivity and arachidonic acid metabolism in type II hyperlipoproteinaemia and its modification by cholesterol-lowering agents. Eicosanoids 1990; 3: 67-73
3 Davi G, Avema M, Catalano I, Barbagallo C, Ganci A, Notarbartolo A, Ciabattoni G, Patrono C. Increased thromboxane biosynthesis in type Ha hypercholesterolemia. Circulation 1992; 85: 1792-1798
4 Prisco D, Rogasi PG, Paniccia R, Coppo M, Abbate R, Gensini GF, Neri Semeri GG. Altered lipid composition and thromboxane A₂formation in platelets from patients affected by type Ha hyperlipoproteinemia. Thromb Res 1988; 50: 593-604
5 Henson PM. Interactions between neutrophils and platelets. Lab Invest 1990; 62: 391-393
6 Gilligan DM, Guetta V, Panza JA, Garcia CE, Quyyumi AA, Cannon III RO. Selective loss of microvascular endothelial function in human hypercholesterolemia. Circulation 1994; 90: 35-41
7 Ross R. The pathogenesis of atherosclerosis: a perspective for 1990s. Nature 1993; 362: 801-809
8 Ricevuti G, Mazzone A, Pasotti D, de Servi S, Specchia G. Role of granulocytes in endothelial injury in coronary heart disease in humans. Atherosclerosis 1991; 9: 1-14
9 Harlan IM. Consequence of leukocyte-vessel wall interactions in inflammatory and immune reactions. Semin Thromb Haemost 1987; 13: 434-444
10 Rapaport SI, Rao VM. Initiation and regulation of tissue factor-dependent blood coagulation. Arterioscl Thromb 1992; 12: 1111-1121
11 WHO Memorandum. Classification of hyperlipidemias and hyperlipoproteinemias. Circulation 1972; 45: 501-508
12 Roschlau P. Enzymatische Bestimmung des Gesamtecholesterins in Serum. Chem Klin Biochem 1974; 12: 226-227
13 Wahalefeld AW. Triglyceride determination after enzymatic hydrolysis. In: ”Methods of enzymatic analysis”. Bergmeyer HU. ed. New York: Academic Press; 1974. 4 1831-1835
14 Lopez-Virella HF, Stone P, Ellis J, Colwell LA. Cholesterol determination in the HDL separated by precipitation with polianions. J Lipid Res 1970; 11: 583-595
15 Becker W, Schafer W, Ziebenbein W. Standardization of immunochemical quantification of human apolipoprotein A and B. La Ricerca Clin Lab 1980; 10: 203-212
16 Albers JJ, Adolphson JL, Hazzard WR. Radioimmunoassay of human plasma Lp(a). J Lipid Res 1977; 18: 331-338
17 Friedewald WT, Levy RJ, Frederickson DS. Estimation of the concentration of low density lipoproteins cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1980; 18: 499-502
18 Avema MR, Barbagallo CM, Galione A, Carroccio A, Labisi M, Marino G, Montalto G, Notarbartolo A. Serum apolipoprotein profile of hypertriglyceridemic patients with chronic renal failure on hemodialysis: a comparison with type IV hyperlipoproteinemic patients. Metabolism 1989; 38: 1-2
19 Ciabattoni G, Maclouf J, Catella F, FitzGerald A, Patrono C. Radioimmunoassay of 11-dehydro-thromboxane B₂in human plasma and urine. Biochim Biophys Acta 1987; 918: 292-297
20 Ciabattoni G, Puglicse F, Davi G, Pierucci A, Simonctti BM, Patrono C. Fractional conversion of thromboxane B₂to urinary H-dehydrothromboxane B₂in man. Bioehim Biophys Acta 1089; 992: 66-70
21 Pelzcr H, Schwarz A, Stuber W. Determination of human prothrombin activation fragment I + 2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 1991; 65: 153-159
22 Mock YA, Shirk A, ten Cate JW, Lamping RJ, Berends F, Bonn JJ J. Laboratory and clinical evaluation of an assay of (hrombin-antithrombin III (TAT) complexes in plasma. Clin (Tern 1988; 34: 2058-2062
23 Neumann S, Gunzer G, Henrieh N, Lang H. PMN elastase assay. Enzyme immunoassay lor human polymorphonuclear elastase complexed with alpha-1-proteinase inhibitor J Clin Chem Clin Biochem 1984; 22: 693-697
24 De Servi S, Mazzone A, Rieevuti G, Fioravanti A, Bramucci E, Angoli L, Ghio S, Specchia D. Granulocyte activation alter coronary angioplasty in humans. Circulation 1990; 82: 140-146
25 Siegel S. Nonparametric Statistics for the Behavioral Sciences. McGrawHill Book Co; New York: 1986. pp 184
26 Tremoli L, Colli S, Maderna P, Baldassarre D, Di Minno G. Hypercholesterolemia and platelets. Semin Thromb Haemost 1993; 19: 115-21
27 Strano A, Davi G, Averna M, Rini GB, Novo S, Di Lede G, Mattina A, Notarbartolo A. Platelet sensitivity to prostacyclin and thromboxane production in hyperlipidemic patients. Thromb Haemost 1982; 48: 18-21
28 Tremoli E, Folco G, Agradi E, Cialli C. Platelet thromboxane and serum cholesterol. Lancet 1979; 1: 107-108
29 Stragliotto H, Camera M, Postiglione A, Sirtori M, Di Minno G, Tremoli E. Functionally abnormal monocytes in hypercholesterolemia. Arterioscl Thromb 1993; 13: 944-950
30 Weissmann G, Smolen JE, Korehak HM. Release of inflammatory mediators from stimulated neutrophils. N Engl J Meil 1980; 303: 27-34
31 Weksler BB, JalTe LA, Brower MS, Cole OF. Human leukocyte cathepsin (i and elastase specifically suppress thrombin-induced prostacyclin production in human endothelial cells. Blood 1989; 74: 1627-1634
32 Reneslo P, Chignard M. Enhancement of cathepsin G-induced platelet activation by leukocyte elastase: consequence for the neutrophil-mediated platelet activation. Blood 1993; 82: 139-144
33 Bauer KA, Rosenberg RD. The pathophysiology of prothrombotic state in humans: Insights gained from studies using markers of hemostatic system activation. Blood 1987; 70: 343-350
34 Merlini PA, Bauer KA, Oltrona L, Ardissino D, Catlaneo M, Belli C, Mannucci PM, Rosenberg RD. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90: 61-68
35 Notarbartolo A, Davi G, Averna M, Barbagallo CM, Ganci A, Giammarresi C, La Placa FP, Patrono C. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscl Thromb 1995; 15: 247-251