Disturbance of synthesis of cholesterol and its precursors in clinically serious conditions
Authors:
P. Vyroubal 1; R. Hyšpler 1; A. Tichá 1; J. Samek 2; J. Cerman 3; E. Havel 3; J. Bajnárek 1; Z. Zadák 1
Authors‘ workplace:
Gerontologická a metabolická klinika Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Luboš Sobotka, CSc.
1; Kardiochirurgická klinika Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Jan Hamer, CSc.
2; Chirurgická klinika Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Alexander Ferko, CSc.
3
Published in:
Vnitř Lék 2011; 57(5): 441-450
Category:
Original Contributions
Overview
Objective:
The aim of the study was to elucidate the role and importance of hypocholesterolemia in clinically serious conditions. It was a monocentric, prospective clinical study.
Material and Methods:
Two groups of patients were recruited to the study – one group were patients with coronary heart disease (CHD), who underwent miniinvasive cardiosurgical operation without extracorporeal circulatio (n = 17) and one group of patients, who sustain polytrauma (n = 19). Thirty six patients were recruited into the study. We performed the determination of sterols (total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols), and their precursors (β-sitosterol, campesterol, lathosterol, skvalen), interleukin IL-6 and cortisol in the blood serum. The short version of ACTH stimulation test was performed. The oxidative burst of granulocytes was evaluated. The blood samples were taken on the day of admission, the first, the fourth and the eighth post-operative and post-traumatic day.
Results:
There was a significant decline of total cholesterol (TC) and LDL-cholesterol level with full recovery during observed period. There was a decline of cholesterol synthesis (lathosterol and lathosterol/cholesterol ratio) together with a decline of total cholesterol. There was a significantly negative correlation between IL-6 level and total cholesterol. Despite no confirmation of disturbance of adrenal function, there was a significantly positive correlation between lathosterol/cholesterol ratio (a de novo cholesterol synthesis marker) and cortisol level after the ACTH stimulation test. There was a significant breakdown of bactericidal function of granulocytes along with a decline of cholesterol level.
Conclusion:
There was decline of endogenous cholesterol synthesis in clinically serious conditions. The cholesterol synthesis rate is negatively influenced by IL-6 level. The rate of endogenous cholesterol synthesis positively correlated with cortisol production by the adrenals and with bactericidal function of granulocytes.
Key words:
hypocholesterolemia – hypolipoproteinemia – SIRS – cytokine – cardiosurgery
Sources
1. Murray RK, Granner DK, Mayes PA et al. Harper’s Biochemistry. 23. Ed. Connecticut: Appleton and Lange 1993.
2. Altmann SW, Davis HR, Zhu I et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004; 303: 1201–1204.
3. Bietrix F, Yan D, Nauze M et al. Accelerated lipid absorption in mice overexpressing intestinal SR-BI J. Biol Chem 2006; 281: 7214–7219.
4. Nauli AM, Nassir F, Zheng H et al. CD 36 is important for chylomicron formation and secretion and may mediate cholesterol uptake in the proximal intestine. Gastroenterology 2006; 131: 1197–1207.
5. Kramer W, Girbig F, Corsiero D et al. Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane. J Biol Chem 2005; 280: 1306–1320.
6. Gibbons GF, Mitropoulos KA, Myant NB. Biochemistry of cholesterol. Amsterdam--New York-Oxford: Elsevier Biomedical Press 1982.
7. Acton S, Rigotti A, Landschulz KT et al. Identification of scavenger receptor SR-BI as a high-density lipoprotein receptor. Science 1996; 271: 518–520.
8. Alvarez C, Ramos A. Lipids, lipoproteins and apoproteins in serum during infection. Clin Chem 1986; 32: 142–145.
9. Elliot DC, Wiles CE 3rd. Low lipid concentrations in critical illness: hypocholesterolemia among trauma patients. Crit Care Med 1997; 25: 1437–1439.
10. Gui D, Spada PL, De Gaetano A et al. Hypocholesterolemia and risk of death in the critically ill surgical patient. Intensive Care Med 1996; 22: 790–794.
11. Wolfram G, Eckard J, Zöllner N. Disturbances of lipoprotein and fatty acid metabolism in patients with heavy injuries (author’s transl). Wien Klin Wochenschr 1980; 58: 1327–1337.
12. Borkowski AJ, Levin S, Delcroix C et al. Blood cholesterol and hydrocortisone production in man: quantitative aspects of the utilization of circulating cholesterol by the adrenals at rest and under adrenocortocotropin stimulation. J Clin Invest 1967; 46: 797–811.
13. Yaguchi H, Tsutsumi K, Shimono K et al. Involvement of high-density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculo-reticularis cells. Life Sci 1998; 62: 1387–1395.
14. Bakalar B, Hyspler R, Pachl J et al. Changes in cholesterol and its precursors during the first days after major trauma. Wien Klin Wochenschr 2003; 115: 775–779.
15. Blanco-Colio LM, Tuñón J, Martín-Ventura JL et al. Anti-inflammatory and immunomodulatory effect of statins. Kidney Int 2003; 63: 12–23.
16. Cailleux A, Cogny M, Allain P. Decrease of isoprene concentrations in humans and in some animal species. Biochem Med Metab Biol 1992; 47: 157–160.
17. Windler E, Ewers-Grabow U, Thiery J et al. The prognostic value of hypocholesterolemia in hospitalized patients. Clin Investig 1994; 72: 939–943.
18. Widimský J, Juráň F, Vaněk P et al. Výrazné zlepšení stavu kardiovaskulární farmakoterapie u nemocných po infarktu myokardu a/nebo revaskularizaci myokardu v roce 1999/2000 v ČR oproti stavu v roce 1995. Cor Vasa 2001; 43: 34–40.
19. Harada K, Shimano H, Kawakami M et al. Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblast. Biochem Biophys Res Comm 1990; 172: 1022–1027.
20. Moran CS, Campbell JH, Campbell GR. Human leukemia inhibitory factor upregulates LDL receptors on liver cells and decreases serum cholesterol in the cholesterol-fed rabbit. Arterioscler Thromb Vasc Biol 1997; 17: 1267–1273.
21. Brass EP, Vetter HV. Interleukin-6, but not tumor necrosis factor-α, increases lipogenesis in rat hepatocyte primary cultures. Biochem J 1994; 301: 193–197.
22. Tietge UJ, Maugeais C, Cain W et al. Overexpression of secretory phospholipase A(2) caused rapid catabolism and altered tissue uptake of high-density lipoprotein cholesterol ester and lipoprotein A-I. J Biol Chem 2000; 275: 10077–10084.
23. Ettinger WH, Varma VK, Sorci-Thomas M et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 1994; 14: 8–13.
24. Gordon BR, Parker TS, Levine DM et al. Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients. Crit Care Med 2001; 29: 1563–1568.
25. Almog Y, Shefer A, Novack V et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004; 110: 880–885.
26. Mülder M, Lombardi P, Jansen H et al. Low density lipoprotein receptor internalizes low density and very low density lipoproteins that are bound to heparan sulfate proteoglycans via lipoprotein lipase. J Biol Chem 1993; 268: 9369–9375.
27. Delgado-Rodrígues M, Medina-Cuadros M, Martinez-Gallego G et al. Total cholesterol, HDL-cholesterol and risk of nosocomial infection: a prospective study in surgical patients. Infect Control Hosp Epidemiol 1997; 18: 9–18.
28. Panousis CG, Zuckerman SH. Interferon-gamma induces downregulation of Tangier disease gene (ATP-binding-cassette transporter-1) in macrophage-derived foam cells. Arterioscler Thromb Vasc Biol 2000; 20: 1565–1571.
29. Freudenberg MA, Bøg-Hansen TC, Back U et al. Interaction of lipopolysaccharides with plasma high-density lipoprotein in rats. Infect Immun 1980; 28: 373–380.
30. Harris HW, Grunfeld C, Feingold KR et al. Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. J Clin Invest 1993; 91: 1028–1034.
31. Hubsch AP, Casas AT, Doran JE. Protective effects of reconstituted high-density lipoprotein in rabbit gram-negative bacteremia models. J Lab Clin Med 1995; 126: 548–558.
32. Goldfarb RD, Parker TS, Levine DM et al. Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis. Am J Physiol Regul Integr Comp Physiol 2003; 284: R550–R557.
33. Pakjrt D, Doran JE, Koster F et al. Antiinflammatory effect of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 1996; 184: 1601–1608.
34. Feingold KR, Soued M, Adi S et al. Tumor necrosis factor increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. Diabetes 1990; 39: 1569–1574.
35. Giovannini I, Boldrini G, Chiarla C et al. Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients. Intensive Care Med 1999; 25: 748–751.
36. van der Voort PH, Gerritsen RT, Bakker AJ et al. HDL-cholesterol level and cortisol response to synacten in critically ill patients. Intensive Care Med 2003; 29: 2199–2203.
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Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2011 Issue 5
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