Thromb Haemost 1985; 54(02): 418-421
DOI: 10.1055/s-0038-1657863
Original Article
Schattauer GmbH Stuttgart

Reduced Prostacyclin Survival After Fasting-Induced Elevation of Plasma Free Fatty Acids

S H Goodnight
The Division of Hematology and Medical Oncology and Section of Nutrition, Department of Medicine, Oregon Health Sciences University, Portland, Oregon, USA
,
S B Inkeles
The Division of Hematology and Medical Oncology and Section of Nutrition, Department of Medicine, Oregon Health Sciences University, Portland, Oregon, USA
,
N L Kovach
The Division of Hematology and Medical Oncology and Section of Nutrition, Department of Medicine, Oregon Health Sciences University, Portland, Oregon, USA
,
W E Connor
The Division of Hematology and Medical Oncology and Section of Nutrition, Department of Medicine, Oregon Health Sciences University, Portland, Oregon, USA
› Author Affiliations
Further Information

Publication History

Received 14 January 1985

Accepted 25 April 1985

Publication Date:
18 July 2018 (online)

Summary

The anti-thrombotic effect of prostacyclin (PGI2) may be determined not only by its synthetic rate but also by its subsequent survival in blood. After its release from the vascular wall, prostacyclin binds to plasma albumin which stabilizes the molecule and prolongs its inhibitory effects on platelets. In vitro studies have shown that free fatty acids compete for the same albumin binding sites and may therefore displace PGI2 and substantially shorten its survival. To see if this competition could also occur in vivo, we produced a three-fold rise of plasma free fatty acid concentrations in ten normal volunteers by four days of fasting, which led to a significant reduction in prostacyclin survival as measured by a functional assay based on inhibition of ADP-induced platelet aggregation. The shortening of prostacyclin survival was associated with evidence of increased platelet reactivity as measured by the circulating platelet aggregate ratio test. Diseases that produce marked elevations of free fatty acids such as acute myocardial infarction may also lead to shortened PGI2 survival with potentiation of platelet mediated thrombosis.

 
  • References

  • 1 Majerus PW. Arachidonate metabolism in vascular disorders. J Clin Invest 1983; 72: 1521-1525
  • 2 Chen Y, Hall ER, McLeod B, Wu KK. Accelerated prostacyclin degradation in thrombotic thrombocytopenic purpura. Lancet 1981; 1: 267-269
  • 3 Brash AR, Jackson EK, Saggese CA, Lawson JA, Oates JA, Fitzgerald GA. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther 1983; 226: 78-87
  • 4 Cho MJ, Allen MA. Chemical stability of prostacyclin (PGI2) in aqueous solutions. Prostaglandins 1978; 15: 943-954
  • 5 Mikhailidis DP, Mikhailidis AM, Woollard ML, Dandona P. Protection of prostacyclin-like activity in human plasma – a non-enzymatic mechanism?. Clin Sci 1982; 62: 177-181
  • 6 Orchard MA, Robinson C. Stability of prostacyclin in human plasma and whole blood: Studies on the protective effect of albumin. Thromb Haemostas 1981; 46: 645-647
  • 7 Pifer DD, Cagen LM, Chesney CM. Stability of prostaglandin I2 in human blood. Prostaglandins 1981; 21: 165-175
  • 8 Mikhailidis DP, Mikhailidis AM, Barradas MA, Dandona P. Effect of nonesterified fatty acids on the stability of prostacyclin activity. Metabolism 1983; 32: 717-721
  • 9 Willems C, Stel HV, van Aken WG, van Mourik JA. Binding and interactivation of prostacyclin (PGI2) by human erythrocytes. Br J Haematol 1983; 54: 43-52
  • 10 Wynalda MA, Fitzpatrick FA. Albumins stabilize prostaglandin I2 . Prostaglandins 1980; 20: 853-861
  • 11 Mikhailidis DP, Mikhailidis AM, Dandona P. Effect of human plasma proteins on stabilization of platelet anti-aggregatory activity of prostacyclin. Ann Clin Biochem 1982; 19: 241-244
  • 12 Spector AA. Fatty acid binding to plasma albumin. J Lipid Res 1975; 16: 165-179
  • 13 Gueriguian JL. Prostaglandin-macromolecule interactions. I. Noncovalent binding of prostaglandins A1, E1, F2a and E2 by human and bovine serum albumins. J Pharmacol Exper Ther 1976; 197: 391-401
  • 14 Lipid Research Clinics Program. Manual of Laboratory Operations, Vol. 1 Lipid and lipoprotein analysis. DHEW publ. no. (NIG) 75–628m. 1974
  • 15 Pinelli A. A new colorimetric method for plasma fatty acid analysis. Clin Chem Acta 1973; 44: 385-390
  • 16 Goodnight SH, Harris WS, Connor WE. The effects of dietary ω3 fatty acids on platelet composition and function in man. A prospective, controlled study. Blood 1981; 58: 880-885
  • 17 Wu KK, Hoak JC. A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Lancet 1974; 2: 294-296
  • 18 Grandstrom E, Kindahl H. Radioimmunoassay of prostaglandins and thromboxanes. Adv Prostaglandin Thrombox Res 1978; 5: 119-210
  • 19 Winder BJ. Single factor experiments having repeated measures on the same elements. In Statistical Principles in Experimental Design. Dashiell JF. (ed) Wallinford: McGraw-Hill, Wallingford CT: 1971: 105-138
  • 20 Kohanna FH, Smith MH, Salzman EW. Do patients with thromboembolic disease have circulating platelet aggregates?. Blood 1984; 64: 205-209
  • 21 Gjesdal K, Nordoy A, Wang H. et al Effects of fasting on plasma and platelet-free fatty acids and platelet function in healthy males. Thromb Haemostas 1976; 36: 325-333
  • 22 Gjesdal K. Platelet function and plasma free fatty acids during acute myocardial infarction and severe angina pectoris. Scand J Haematol 1976; 17: 205-212
  • 23 Maca RD, Hoak JC. Endothelial injury and platelet aggregation associated with acute lipid mobilization. Lab Invest 1974; 30: 589-595
  • 24 Hoak JC, Warner ED, Connor WE. Platelets, fatty acids and thrombosis. Circ Res 1967; 20: 11-17
  • 25 Opie LH, Tansey M, Kennelly BM. Proposed metabolic vicious circle in patients with large myocardial infarcts and high plasma-free-fatty-acid concentrations. Lancet 1977; 2: 890-892
  • 26 Vik-Mo H, Mjos OD. Influence of free fatty acids on myocardial oxygen consumption and ischemic injury. Am J Cardiol 1981; 48: 361-365
  • 27 Oliver MF, Kurien VA, Greenwood TW. Relations between serum-free-fatty-acids and arrhythmias and death after acute myocardial infarction. Lancet 1968; 1: 710-715
  • 28 Tansey JB, Opie LH. Relation between plasma free fatty acids and arrhythmias within the first twelve hours of acute myocardial infarction. Lancet 1983; 2: 419-421