SpringerLink
Log in

Cholesterol efflux and the effect of combined treatment with niacin and chromium on aorta of hyperlipidemic rat

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Endothelial cells may play a potential role in cholesterol efflux from peripheral tissues to liver. Cholesterol efflux from cells is essential for activation of the reverse cholesterol transport pathway and cardiovascular health. One of the cholesterol transporters is steroidogenic acute regulatory protein (StAR) which promotes intramitochondrial delivery of cholesterol to the cholesterol side-chain cleavage system. The aim of the present study was to determine the effects of a niacin–chromium complex on aortas of hyperlipidemic rats and on the cholesterol efflux from aorta endothelial cells by examination under light and transmission electron microscopes and evaluating the StAR immunoreactivity, respectively. Aorta lipid peroxidation (LPO) and glutathione (GSH) levels were determined by spectrophotometric methods. After treating hyperlipidemic animals with the complex, the StAR immunoreactivity in endothelial cells increased to achieve cholesterol homeostasis and efflux. Combined treatment with niacin and chromium resulted in an inhibition in the mast cell secretion and a decrease in lipid vacuole size in unilocular adipose tissue surrounding aorta, as well as in a decrease in morphological degenerations observing in aorta of hyperlipidemic rats. Aorta LPO levels increased and GSH levels decreased in the hyperlipidemic group, whereas treatment with niacin and chromium reversed these effects. In conclusion, this study reveals that combined treatment with niacin and chromium prevents the morphological and biochemical changes observed in thoracic aorta of hyperlipidemic rats, and may regulate effectively cardiovascular diseases inducing an increase in StAR levels on endothelial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Major AS, Dove DE, Ishiguro H, Su YR, Brown AM, Liu L, Carter KJ, Linton MF, Fazio S (2001) Increased cholesterol efflux in apolipoprotein AI (ApoAI)-producing macrophages as a mechanism for reduced atherosclerosis in apo AI (−/−) mice. Atheroscler Thromb Vasc Biol 21:1790–1795

    Article  CAS  Google Scholar 

  2. Reiss AB, Martin KO, Javitt NB, Martin DW, Grossi EA, Galloway AC (1994) Sterol 27-hydroxylase: high levels of activity in vascular endothelium. J Lipid Res 35:1026–1030

    PubMed  CAS  Google Scholar 

  3. Javitt NB (1994) Bile acid synthesis from cholesterol: regulatory and auxilary pathways. FASEB J 8:1308–1311

    PubMed  CAS  Google Scholar 

  4. Bjorkhem I (2002) Do oxysterols control cholesterol homeostasis? J Clin Invest 110:725–730

    Article  PubMed  CAS  Google Scholar 

  5. Babiker A, Andersson O, Lund E, **u RJ, Deeb S, Reshef A, Leitersdof E, Diczfalusy U, Bjorkhem I (1997) Elimination of cholesterol and macrophages and endothelial cells by the sterol 27-hydroxylase mechanism: comparison with high density lipoprotein-mediated reverse cholesterol transport. J Biol Chem 272:26253–26261

    Article  PubMed  CAS  Google Scholar 

  6. Janowski BA, Willy PJ, Devi TR, Talck JR, Mangelsdorf DJ (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature (London) 383:728–731

    Article  CAS  Google Scholar 

  7. Costet P, Luo Y, Wang N, Tall AR (2000) Sterol-dependent transactivation of the human ABC1 promoter by LXR/RXR. J Biol Chem 275:28240–28245

    PubMed  CAS  Google Scholar 

  8. Venkateswaren A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P (2000) Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXRalfa. Proc Natl Acad Sci USA 97:12097–12102

    Article  Google Scholar 

  9. Maxfield FR, Wustner D (2002) Intracellular cholesterol transport. J Clin Invest 110:891–898

    Article  PubMed  CAS  Google Scholar 

  10. Jefcoate C (2002) High-flux mitochondrial cholesterol trafficking, a specialized function of the adrenal cortex. J Clin Invest 110:881–890

    Article  PubMed  CAS  Google Scholar 

  11. Hall EA, Ren S, Hylemon PB, Agudo DR, Redford K, Marques D, Kang D, Gil G, Pandak WM (2005) Detection of the steroidogenic acute regulatory protein, StAR, in human liver cells. Biochim Biophys Acta 1733:111–119

    PubMed  CAS  Google Scholar 

  12. Ning Y, Chen S, Li X, Ma Y, Zhao F, Yin L (2006) Cholesterol, LDL, and 25-hydroxycholesterol regulate expression of the steroidogenic acute regulatory protein in microvascular endothelial cell line (bEnd.3). Biochem Biophys Res Commun 342:1249–1256

    Article  PubMed  CAS  Google Scholar 

  13. Pandak WM, Ren S, Marques D, Hall E, Redford K, Mallonee D, Bohdan P, Heuman D, Gil G (2002) Hylemon P. Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. J Biol Chem 277:48158–48164

    Article  PubMed  CAS  Google Scholar 

  14. Ren S, Hylemon PB, Marques D, Hall E, Redford K, Gil G, Pandak WM (2004) Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis. J Lipid Res 45:2123–2131

    Article  PubMed  CAS  Google Scholar 

  15. Ledwozyw L, Michalak J, Stepien A, Kadziolka A (1986) The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta 155:275–284

    Article  PubMed  CAS  Google Scholar 

  16. Beutler E (1975) Glutathione in red blood cell metabolism: a manual of biochemical methods, 2nd edn. Grunne and Stratton, New York

    Google Scholar 

  17. Linsel-Nitschke P, Tall AR (2005) HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov 4:193–205

    Article  PubMed  CAS  Google Scholar 

  18. Genest JJ, McNamara JR, Salem DN, Schaefer EJ (1991) Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 67:1185–1189

    Article  PubMed  CAS  Google Scholar 

  19. Kashyap ML (1989) Basic considerations in the reversal of atherosclerosis: significance of high density lipoproteins in stimulating reverse cholesterol transport. Am J Cardiol 63:56–59

    Article  Google Scholar 

  20. DiPalma JR, Thayer WS (1991) Use of niacin as a drug. Annu Rev Nutr 11:169–187

    Article  PubMed  CAS  Google Scholar 

  21. Bolkent S, Yanardag R, Bolkent S, Doger MM (2004) Beneficial effects of combined treatment with niacin and chromium on the liver of hyperlipidemic rats. Biol Trace Elem Res 101:219–230

    Article  PubMed  CAS  Google Scholar 

  22. Inceli MS, Bolkent S, Doger MM, Yanardag R (2007) The effects of combined treatment with niacin and chromium on the renal tissues of hyperlipidemic rats. Mol Cell Biochem 294:37–44

    Article  PubMed  CAS  Google Scholar 

  23. Urberg M, Benyi J, John R (1988) Hypocholesterolemic effects of nicotinic acid and chromium supplementation. J Fam Pract 27:603–606

    PubMed  CAS  Google Scholar 

  24. Bagchi D, Stohs SJ, Down BW, Bagchi M, Preuss HG (2002) Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 180:5–22

    Article  PubMed  CAS  Google Scholar 

  25. Preuss HG, Anderson RA (1998) Chromium updates: examining recent literature 1997–1998. Curr Opin Clin Nutr Metab Case 1:509–512

    Article  CAS  Google Scholar 

  26. Wang MM, Fox EA, Stoecker BJ, Menendez CE, Chan SB (1989) Serum cholesterol of adults suplemented with Brewer’s yeast or chromium chloride. Nutr Res 9:989–998

    Article  CAS  Google Scholar 

  27. Schroeder HA, Vinton WH, Balassa JJ (1962) Effect of chromium, cadmium and lead on serum cholesterol of rats. Proc Soc Exp Biol Med 109:859–860

    PubMed  CAS  Google Scholar 

  28. Altschul R, Hoffer A, Steohen JD (1955) Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys 54:558–559

    Article  CAS  Google Scholar 

  29. Grundy SM, Mok HY, Zech L, Berman M (1981) Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. J Lipid Res 22:24–36

    PubMed  CAS  Google Scholar 

  30. Kashyap ML (1988) Mechanistic studies of high density lipoproteins. Am J Cardiol 82:42–48

    Article  Google Scholar 

  31. Sakai T, Vai**ath S, Kamanna S, Kashyap ML (2001) Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfruction of HDL, in patients with low HDL cholesterol. Atheroscler Thromb Vasc Biol 21:1783–1797

    Article  CAS  Google Scholar 

  32. Zambon A, Hokanson J, Brown BG, Brunzel SD (1999) Evidence for a new pathophysiological mechanism for coronary artery disease regression, hepatic lipase-mediated changes in LDL density. Circulation 99:1959–1964

    PubMed  CAS  Google Scholar 

  33. Gardner CD, Chatterjee LM, Carlson JJ (2001) The effect of a garlic preparation on plasma lipid levels in moderately hypercholesterolemic adults. Atherosclerosis 154:213–220

    Article  PubMed  CAS  Google Scholar 

  34. Khanna AK, Rizvi F, Chander R (2002) Lipid lowering activity of Phyllanthus niruri in hyperlipidemic rats. J Ethnopharmacol 82:19–22

    Article  PubMed  CAS  Google Scholar 

  35. Devi R, Sharma DK (2004) Hypolipidemic effect of different extracts of Clerodendron colebrookianum Walp in normal and high-fat diet fed rats. J Ethnopharmacol 90:63–68

    Article  PubMed  Google Scholar 

  36. Lindstedt KA, Leskinen MJ, Kovanen PT (2004) Proteolysis of the pericellular matrix: a novel element determining cell survival and death in the pathogenesis of plaque erosion and rupture. Atheroscler Thromb Vasc Biol 24:1350–1358

    Article  CAS  Google Scholar 

  37. Lee M, Lindstedt KA, Kovanen PT (1992) Mast cells-mediated inhibition of reverse cholesterol transport. Atheroscler Thromb 12:1329–1335

    CAS  Google Scholar 

  38. Lee M, Kovanen PT (2006) Mast cell proteases: physiological tools to study functional significance of high density lipoproteins in the initiation of reverse cholesterol transport. Atheroscler 189:8–18

    Article  Google Scholar 

  39. Yanardag R, Peksel A, Yesilyaprak B, Doger MM, Arisan-Atac I (2005) Effects of a combination of niacin and chromium (III)-chloride on the skin and lungs of hyperlipemic rats. Biol Trace Elem Res 103:249–260

    Article  PubMed  CAS  Google Scholar 

  40. A-Atac I, Peksel A, Yanardag R, Sokmen BB, Doger MM, Bilen ZG (2006) The effect of combined treatment with niacin and chromium (III) chloride on the different tissues of hyperlipidemic rats. Drug Chem Toxicol 29:363–377

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Science, Department of Biology, Zoology Section, Istanbul University, Vezneciler, 34459, Istanbul, Turkey

    Songul Suren Castillo & Sehnaz Bolkent

  2. Faculty of Engineering, Department of Chemistry, Istanbul University, Avcılar, 34320, Istanbul, Turkey

    M. Mutluhan Doger & Refiye Yanardag

Authors
  1. Songul Suren Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Mutluhan Doger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sehnaz Bolkent
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Refiye Yanardag
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Songul Suren Castillo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suren Castillo, S., Doger, M.M., Bolkent, S. et al. Cholesterol efflux and the effect of combined treatment with niacin and chromium on aorta of hyperlipidemic rat. Mol Cell Biochem 308, 151–159 (2008). https://doi.org/10.1007/s11010-007-9623-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9623-2

Keywords

Search

Navigation