**Author details**

Maaike Kockx

*Macrophage Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, Australia* 

Leonard Kritharides\*

*Macrophage Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, Australia* 

*Department of Cardiology, Concord Repatriation General Hospital, University of Sydney, Sydney, Australia* 

### **6. References**


<sup>\*</sup> Corresponding Author

[6] Raine AE, Carter R, Mann JI, Morris PJ (1988) Adverse effect of cyclosporin on plasma cholesterol in renal transplant recipients. Nephrol Dial Transplant 3: 458-463.

348 Lipoproteins – Role in Health and Diseases

therapy alone [100,101].

**5. Conclusions** 

**Author details** 

Leonard Kritharides\*

Maaike Kockx

*Australia* 

*Australia* 

*Australia* 

 \*

**6. References** 

Corresponding Author

Transplantation 63: 331-338.

Endocrinol Metab Clin North Am 40: 409-417, ix.

Transplant 2: 807-818.

Clin Biochem 25: 379-386.

absorption in the small intestine [99]. To that point though, various studies showed effective LDL-C lowering in liver, cardiac and renal transplant recipients [99]. Although, drug-drug interaction between CsA and ezetimibe were suggested (See [88]), CsA levels in studied transplant patients were not affected by combined ezetimibe use (reviewed in [99]). Coadministration of ezetimibe with (low-dose) statins has been found to effectively reduce high plasma cholesterol levels in transplant recipients and may be useful in patients that resistant to high-dose statin or where target plasma lipid levels can not be achieved by statin

CsA-induced hyperlipidemia is well established and remains a significant clinical issue. CsA potentially affects many aspects of lipid and lipoprotein metabolism and the precise underlying mechanism(s) causing dyslipidemia are still unclear. Further mechanistic studies may lead to the generation immunosuppressants that do not cause hyperlipidemia or may

*Macrophage Biology Group, Centre for Vascular Research, University of New South Wales, Sydney,* 

*Macrophage Biology Group, Centre for Vascular Research, University of New South Wales, Sydney,* 

*Department of Cardiology, Concord Repatriation General Hospital, University of Sydney, Sydney,* 

[1] Kobashigawa JA, Kasiske BL (1997) Hyperlipidemia in solid organ transplantation.

[2] Miller LW (2002) Cardiovascular toxicities of immunosuppressive agents. Am J

[3] Strohmayer EA, Krakoff LR (2011) Glucocorticoids and cardiovascular risk factors.

[4] Lopez-Miranda J, Perez-Jimenez F, Torres A, Espino-Montoro A, Gomez P, et al. (1992) Effect of cyclosporin on plasma lipoproteins in bone marrow transplantation patients.

[5] Ballantyne CM, Podet EJ, Patsch WP, Harati Y, Appel V, et al. (1989) Effects of

cyclosporine therapy on plasma lipoprotein levels. JAMA 262: 53-56.

help to develop strategies to effectively target CsA-induced hyperlipidemia.


[37] Akhlaghi F, Trull AK (2002) Distribution of cyclosporin in organ transplant recipients. Clin Pharmacokinet 41: 615-637.

350 Lipoproteins – Role in Health and Diseases

Pharmacol Rev 58: 342-374.

Clin Biochem 25: 387-394.

J Lab Clin Med 125: 222-227.

2528.

341: 268-270.

2281-2287.

Kidney Int Suppl 71: S235-237.

transfers. J Biol Chem 280: 21612-21621.

heterogeneity. J Lipid Res 43: 1363-1379.

nonvascular mortality. JAMA 302: 412-423.

renal transplant recipients. Transplant Proc 34: 370-372.

metabolism. Arterioscler Thromb Vasc Biol 17: 3542-3556.

[21] Kontush A, Chapman MJ (2006) Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis.

[22] Rosenson RS, Brewer HB, Jr., Chapman MJ, Fazio S, Hussain MM, et al. (2011) HDL measures, particle heterogeneity, proposed nomenclature, and relation to

[23] Zheng H, Kiss RS, Franklin V, Wang MD, Haidar B, et al. (2005) ApoA-I lipidation in primary mouse hepatocytes. Separate controls for phospholipid and cholesterol

[24] Lopez-Miranda J, Perez-Jimenez F, Gomez-Gerique JA, Espino-Montoro A, Hidalgo-Rojas L, et al. (1992) Effect of cyclosporin on plasma lipoprotein lipase activity in rats.

[25] Espino A, Lopez-Miranda J, Blanco-Cerrada J, Zambrana JL, Aumente MA, et al. (1995) The effect of cyclosporine and methylprednisolone on plasma lipoprotein levels in rats.

[26] Zeljkovic A, Vekic J, Spasojevic-Kalimanovska V, Jelic-Ivanovic Z, Peco-Antic A, et al. (2011) Characteristics of low-density and high-density lipoprotein subclasses in

[27] Berneis KK, Krauss RM (2002) Metabolic origins and clinical significance of LDL

[28] Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, et al. (2009) Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and

[29] Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, et al. (2009) Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 361: 2518-

[30] Fonseca I, Queiros J, Costa S, Santos MJ, Henriques AC, et al. (2002) Lipoprotein(A) in

[31] Innocenti M, Lorenzetti M, Naldi F, Paleologo G, Pasquariello A, et al. (1998) Evaluation

[32] Black IW, Wilcken DE (1992) Decreases in apolipoprotein(a) after renal transplantation:

[33] Webb AT, Reaveley DA, O'Donnell M, O'Connor B, Seed M, et al. (1993) Does cyclosporin increase lipoprotein(a) concentrations in renal transplant recipients? Lancet

[34] Packard CJ, Shepherd J (1997) Lipoprotein heterogeneity and apolipoprotein B

[35] Rajman I, Harper L, McPake D, Kendall MJ, Wheeler DC (1998) Low-density lipoprotein subfraction profiles in chronic renal failure. Nephrol Dial Transplant 13:

[36] Quaschning T, Mainka T, Nauck M, Rump LC, Wanner C, et al. (1999) Immunosuppression enhances atherogenicity of lipid profile after transplantation.

of lipoprotein A in renal transplant recipients. Transplant Proc 30: 2048.

implications for lipoprotein(a) metabolism. Clin Chem 38: 353-357.

atherosclerotic cardiovascular events. Clin Chem 57: 392-410.

pediatric renal transplant recipients. Transpl Int 24: 1094-1102.


[69] Souidi M, Parquet M, Ferezou J, Lutton C (1999) Modulation of cholesterol 7alphahydroxylase and sterol 27-hydroxylase activities by steroids and physiological conditions in hamster. Life Sci 64: 1585-1593.

352 Lipoproteins – Role in Health and Diseases

392-397.

Metabolism 42: 678-683.

Mol Med 86: 171-183.

Mol Endocrinol 37: 367-373.

subjects. J Lipid Res 40: 1194-1199.

120: 109-122.

[53] Tory R, Sachs-Barrable K, Hill JS, Wasan KM (2008) Cyclosporine A and Rapamycin induce in vitro cholesteryl ester transfer protein activity, and suppress lipoprotein

[54] Atger V, Leclerc T, Cambillau M, Guillemain R, Marti C, et al. (1993) Elevated high density lipoprotein concentrations in heart transplant recipients are related to impaired plasma cholesteryl ester transfer and hepatic lipase activity. Atherosclerosis 103: 29-41. [55] Kockx M, Jessup W, Kritharides L (2010) Cyclosporin A and atherosclerosis--cellular

[56] Rayyes OA, Wallmark A, Floren CH (1996) Cyclosporine inhibits catabolism of low-

[57] Gueguen Y, Ferrari L, Souidi M, Batt AM, Lutton C, et al. (2007) Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase. Basic Clin Pharmacol Toxicol 100:

[58] Lopez-Miranda J, Vilella E, Perez-Jimenez F, Espino A, Jimenez-Pereperez JA, et al. (1993) Low-density lipoprotein metabolism in rats treated with cyclosporine.

[59] Le Goff W, Peng DQ, Settle M, Brubaker G, Morton RE, et al. (2004) Cyclosporin A traps ABCA1 at the plasma membrane and inhibits ABCA1-mediated lipid efflux to

[60] Lorenzi I, von Eckardstein A, Cavelier C, Radosavljevic S, Rohrer L (2008) Apolipoprotein A-I but not high-density lipoproteins are internalised by RAW macrophages: roles of ATP-binding cassette transporter A1 and scavenger receptor BI. J

[61] Karwatsky J, Ma L, Dong F, Zha X (2009) Cholesterol efflux to apoA-I in ABCA1 expressing cells is regulated by Ca2+ dependent-calcineurin signaling. J Lipid Res. [62] Emeson EE, Shen ML (1993) Accelerated atherosclerosis in hyperlipidemic C57BL/6

[63] Maitra U, Parks JS, Li L (2009) An innate immunity signaling process suppresses macrophage ABCA1 expression through IRAK-1-mediated downregulation of retinoic

[64] Zheng XL, Wong NC (2006) Cyclosporin A inhibits apolipoprotein AI gene expression. J

[65] Van Summeren A, Renes J, Bouwman FG, Noben JP, van Delft JH, et al. (2011) Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci

[66] von Eckardstein A, Huang Y, Assmann G (1994) Physiological role and clinical relevance of high-density lipoprotein subclasses. Curr Opin Lipidol 5: 404-416. [67] Anderson KE, Kok E, Javitt NB (1972) Bile acid synthesis in man: metabolism of 7 hydroxycholesterol- 14 C and 26-hydroxycholesterol- 3 H. J Clin Invest 51: 112-117. [68] Duane WC, Javitt NB (1999) 27-hydroxycholesterol: production rates in normal human

apolipoprotein A-I. Arterioscler Thromb Vasc Biol 24: 2155-2161.

mice treated with cyclosporin A. Am J Pathol 142: 1906-1915.

acid receptor alpha and NFATc2. Mol Cell Biol 29: 5989-5997.

density lipoproteins in HepG2 cells by about 25%. Hepatology 24: 613-619.

lipase activity in human plasma. Int J Pharm 358: 219-223.

pathways in atherogenesis. Pharmacol Ther 128: 106-118.

