Circulating bactericidal/permeability-increasing protein (BPI) is associated with serum lipids and endothelial function

Eduardo Esteve; Antoni Castro; Jose Maria Moreno; Joan Vendrell; Wifredo Ricart; José Manuel Fernández-Real

doi:10.1160/TH09-08-0596

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 780-787
DOI: 10.1160/TH09-08-0596

Endothelium and Vascular Development

Schattauer GmbH

Circulating bactericidal/permeability-increasing protein (BPI) is associated with serum lipids and endothelial function

Authors

Eduardo Esteve

¹Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain and CIBERobn Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, and CIBERDEM, Instituto de Salud Carlos III, Spain
Antoni Castro

¹Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain and CIBERobn Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, and CIBERDEM, Instituto de Salud Carlos III, Spain
Jose Maria Moreno

¹Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain and CIBERobn Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, and CIBERDEM, Instituto de Salud Carlos III, Spain
Joan Vendrell

²Research Unit, University Hospital of Tarragona ’Joan XXIII’, Institut Pere Virgili, Tarragona, Spain
Wifredo Ricart

¹Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain and CIBERobn Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, and CIBERDEM, Instituto de Salud Carlos III, Spain
José Manuel Fernández-Real

¹Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain and CIBERobn Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, and CIBERDEM, Instituto de Salud Carlos III, Spain

Abstract

Summary

Bactericidal/permeability-increasing protein (BPI), a major constituent of neutrophils that possesses anti-inflammatory properties, shows a structure similar to some proteins implicated in lipid metabolism. We evaluated circulating BPI as a biomarker of endothelial function and lipid metabolism. Circulating BPI concentrations (ELISA) and serum lipids were measured in 202 Caucasian non-smoking men. In a subgroup of 91 consecutive subjects brachial vascular reactivity (high resolution external ultrasound) was assessed. Plasma BPI concentrations were positively associated with total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) (r= 0.203, 0.204 and 0.18; all p<0.05, respectively). In a multiple linear regression analysis, BPI levels were independent contributors to the variance of HDL-C, total cholesterol and LDL-cholesterol after adjusting for age, body mass index and glucose tolerance status. Plasma BPI concentration correlated positively with endothelium-dependent vasodilatation (r=0.277; p<0.05) and HDL-C (r=0.36; p<0.05) in subjects with normal glucose tolerance. In conclusion, circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function.

Keywords

Inflammation - HDL-cholesterol - bactericidal/permeability-increasing protein - cholesteryl ester transfer protein - infection - cytokines

Full Text

References

References
1 Schatz IJ, Masaki K, Yano K. et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001; 358: 351-355.
2 Jacobs DR, Blackburn H, Higgins M. et al. Report of the conference on low blood cholesterol: mortality associations. Circulation 1992; 86: 1046-1060.
3 Iribarren C, Reed DM, Chen R. et al. Low serum cholesterol and mortality. Which is the cause and which is the effect? Circulation 1995; 92: 2396-2403.
4 Meilahn EN. Low serum cholesterol. Hazardous to health? Circulation 1995; 92: 2365-2366.
5 Bingle CD, Craven CJ. Meet the relatives: a family of BPI- and LBP-related proteins. Trends Immunol 2004; 25: 53-55.
6 Weiss J, Olsson I. Cellular and subcellular localization of the bactericidal/ permeability-increasing protein of neutrophils. Blood 1987; 69: 652-659.
7 Elsbach P. The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense. J Leukoc Biol 1998; 64: 14-18.
8 Beamer LJ, Carroll SF, Eisenberg D. Crystal structure of human BPI and two bound phospholipids at 2.4 Angstrom resolution. Science 1997; 276: 1861-1864.
9 Megia A, Gallart L, Fernández-Real JM. et al. Mannose-binding lectin gene polymorphism is associated with gestational diabetes mellitus. J Clin Endocrinol Metab 2004; 89: 5081-5087.
10 Fernández-Real JM, Broch M, Richart C. et al. CD14 monocyte receptor, involved in the inflammatory cascade, and insulin sensitivity. J Clin Endocrinol Metab 2003; 88: 1780-1784.
11 Chen Z, Peto R, Collins R. et al. Serum cholesterol concentration and coronary heart disease in populations with low cholesterol concentrations. Br Med J 1993; 303: 276-282.
12 Chien JY, Jerng JS, Yu CJ. et al. Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit. Care Med 2005; 33: 1688-1693.
13 Vermont CL, den Brinker M, Kakeci N. et al. Serum lipids and disease severity in children with severe meningococcal sepsis. Crit Care Med 2005; 33: 1610-1615.
14 Schultz H, Heintz H, van Zandbergen G. et al. ANCA against the bactericidal/permeability increasing protein (BPI-ANCA) can compromise the antibiotic function of BPI in a Wegener’s granulomatosis patient. Clin. Exp. Rheumatol 2003; 21: 763-736.
15 Alexander S, Bramson J, Foley R. et al. Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein. Blood 2004; 103: 93-99.
16 Wong HR, Doughty LA, Wedel N. et al. JA. Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome. J Pediatr Infect Dis 1995; 14: 1087-1091.
17 Fernandez-Real JM, Ricart W. Cholesterol and all-cause mortality in Honolulu. Lancet 2001; 358: 1906-1907.
18 Forette B, Tortrat D, Wolmark Y. Cholesterol as a risk factor for mortality in elderly women. Lancet 1989; 01: 868-870.
19 Harris HW, Grunfeld C, Feingold KR. et al. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. J Clin Invest 1990; 86: 696-702.
20 Vreugdenhil ACE, Snoek AMP, van’t Veer C. et al. LPS-binding protein circulates in associaiton with apo-B containing lipoproteins and enhances endotoxin-LDL/ VLDL interaction. J Clin Invest 2001; 107: 225-234.
21 Gubern C, López-Bermejo A, Biarnés J. et al. Natural antibiotics and insulin sensitivity: the role of bactericidal/permeability-increasing protein. Diabetes 2006; 55: 216-224.
22 Weiss J, Elsbach P, Shu C. et al. Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria. J Clin Invest 1992; 90: 1122-1130.
23 Arditi M, Zhou J, Huang SH. et al. Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury. Infect Immun 1994; 62: 3930-3936.
24 Van der Schaft DW, Toebes EA, Haseman JR. et al. Bactericidal/permeability-increasing protein (BPI) inhibits angiogenesis via induction of apoptosis in vascular endothelial cells. Blood 2000; 96: 176-181.
25 Ciornei CD, Egesten A, Engström M. et al. Bactericidal/permeability-increasing protein inhibits endotoxin-induced vascular nitric oxide synthesis. Acta Anaesthesiol Scand 2002; 46: 1111-1118.
26 Hardardottir I, Moser AH, Fuller J. et al. Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters. J Clin Invest 1996; 97: 2585-2592.
27 Jiang XC, Bruce C. Regulation of murine plasma phospholipid transfer protein activity and mRNA levels by lipopolysaccharide and high cholesterol diet. J Biol Chem 1995; 270: 17133-17138.
28 Jiang XC, Bruce C, Mar J. et al. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest 1999; 103: 907-914.