Effect of LDL-apheresis on plasma lipids, chitotriosidase and anti-oxLDL antibodies in heterozygous familial hypercholes-terolemia

DOI: 10.4236/jbise.2009.27072   PDF   HTML     4,760 Downloads   8,272 Views   Citations


Forty four consecutive subjects aged 29-58 years (21 males and 23 females) with a clinical diagnosis of heterozygous familial hypercholesterolemia periodically treated every 30 days with LDL-apheresis for statin resistance, were enrolled in this study. A lipid profile was obtained immediately before starting LDL-apheresis, a second profile was obtained within four hours after LDL-apheresis. Chit activity and anti-oxLDL levels were determined with appropriate methods in all patients before and after LDL- apheresis. Total cholesterol, LDL-cholesterol, HDL- cholesterol and triglycerides decreased significantly after LDL-apheresis, while the variations of Chit activity and anti-oxLDL were not significant after LDL-apheresis. The correlation between Chit and total cholesterol was negative (r= –0.44 and –0.50 res- pectively) before and after LDL-apheresis as between Chit and LDL-cholesterol (r= –0.45 and –0.55 respectively). Anti-oxLDL concentration before and after LDL-apheresis positively correlated with Chit activity (r= 0.52 and r = 0.63 respectively), negatively with total cholesterol (r= –0.33 and r = –0.35 res- pectively) and with LDL (r = –0.32 and r = –0.21 respectively). We think that removing LDL with LDL-apheresis the anti-oxLDL/oxLDL ratio could increase and the excess of anti-oxLDL could induce macrophage activation through the surface Fc receptors. Alternatively with high levels of LDL- cholesterol, the deposition of foam cells represent the characteristic evolution of atherosclerosis process. Macrophage activation in the heterozygous familial hypercholesterolemia could represent an attempt for re-modeling the vessel wall, reducing the growth of lipid plaques.

Share and Cite:

Musumeci, M. , Pappalardo, F. , Tonolo, G. , Torrisi, F. , Gullo, F. and Musumeci, S. (2009) Effect of LDL-apheresis on plasma lipids, chitotriosidase and anti-oxLDL antibodies in heterozygous familial hypercholes-terolemia. Journal of Biomedical Science and Engineering, 2, 499-505. doi: 10.4236/jbise.2009.27072.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Goldstein, J. L., Hobbs, H. H., and Brown, M. S., (2001) Familial hypercholesterolemia, The Metabolic and Molecular Basis of Inherited Disease, Scriver CR, Beaudet, A. L., Sly, W. S., Valle D, eds., McGraw-Hill, New York, 2863?2913.
[2] Ross, R., (1999) Atherosclerosis: An inflammatory disease, N. Engl. J. Med., 340, 115?126.
[3] Civeira, F., (2004) Guidelines for the diagnosis and management of heterozygous familial hypercholestero- lemia, Atherosclerosis, 173, 55?68.
[4] Kern, F., (1990) Cholesterol metabolism, LDL, and the LDL receptor, Edited by Myant NB, Academic press, NewYork, 465.
[5] Shoji, T., Nishizawa, Y., Fukumoto, M., Shimamura, K., Kimura J., Kanda, H., et al., (2000) Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis; 148, 171?7.
[6] Bertolini, S., Cantafora, A., Averna, M., Cortese, C., Motti, C., Martini, S., et al., (2000) Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype, Arterioscler Thromb Vasc Biol, 20, 41?52.
[7] Hollak, C. E., van Weely, S., van Oers, M. H., and Aerts, J. M., (1994) Marked elevation of plasma chitotriosidase activity, A novel hallmark of Gaucher disease, J. Clin. Invest., 93, 1288?1292.
[8] Boot, R. G., van Achterberg, T. A., van Aken, B. E., Renkema, G. H., Jacobs, M. J., Aerts, J. M., et al., (1999) Strong induction of members of the chitinase family of proteins in atherosclerosis: Chitotriosidase and human cartilage gp-39 expressed in lesion macrophages, Arterio- scler Thromb Vasc Biol, 19, 687?694.
[9] Malaguarnera, L., Di Rosa, M., Zambito, A. M., dell'Ombra, N., Nicoletti, F., and Malaguarnera, M., (2006) Chitotrio- sidase gene expression in Kupffer cells from patients with non- alcoholic fatty liver disease, Gut, 55, 1313?1320.
[10] Artieda, M., Cenarro, A., Ga?án, A., Jericó, I., Gonzalvo, C., Casado, J. M., et al., (2003) Serum chitotriosidase activity is increased in subjects with atherosclerosis disease, Arterioscler Thromb Vasc Biol., 23, 1645?1652.
[11] Artieda, M., Cenarro, A., Ga?án, A., Lukic, A., Moreno, E., Puzo, J., et al., (2007) Serum chitotriosidase activity, a marker of activated macrophages, predicts new cardiovascular events independently of C-Reactive Protein, Cardiology, 108, 297?306.
[12] Hansson, G. K., (2005) Inflammation, atherosclerosis, and coronary artery disease, N. Engl. J. Med., 352, 1685?1695.
[13] van Eijk, M., van Roomen, C. P., Renkema, G. H., Bussink, A. P., Andrews, L., Blommaart, E. F., et al., (2005) Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity, Int. Immunol., 17, 1505?12.
[14] Shaw, P. X., H?rkk?, S., Tsimikas, S., Chang, M. K., Palinski, W., Silverman, G. J., et al., (2001) Human-derived anti-oxidized LDL autoantibody blocks uptake of oxi- dized LDL by macrophages and localizes to atheroscle- rotic lesions in vivo, Arterioscler Thromb Vasc Biol, 21, 1333?9.
[15] Bláha, M., Cermanová, M., Bláha, V., Blazek, M., Maly, J., Siroky, O., et al., (2007) Safety and tolerability of long lasting LDL-apheresis in familial hyperlipopro- teinemia. Ther Apher Dial, 11, 9?15.
[16] Hixson, J. E. and Vernier, D. T., (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI, J. Lipid. Res., 31, 545–8.
[17] Tsukamoto, K., Watanabe, T., Matsushima, T., Kinoshita, M., Kato, H., Hashimoto, Y., Kurokawa, K., and Teramoto, T., (1993) Determination by PCR-RFLP of apo E genotype in a Japanese population, J. Lab. Clin. Med., 121, 598?602.
[18] Hulthe, J., Wikstrand, J., Lidell, A., Wendelhag, I., Hansson, G. K., and Wiklund, O., (1998) Antibody titers against oxidized LDL are not elevated in patients with familial hypercholesterolemia, Arterioscler Thromb Vasc Biol, 18, 1203?1211.
[19] Tinahones, F. J., Gomez-Zumaquero, J. M., Rojo- Martinez, G., Cardona, F., Esteva de Antonio, I. E., Ruiz de Adana, M. S., et al., (2002) Increased levels of anti-oxidized low-density lipoprotein antibodies are associated with reduced levels of cholesterol in the general population, Metabolism, 51, 429?31.
[20] Tinahones, F. J., Gomez-Zumaquero, J. M., Garrido- Sanchez, L., Garcia-Fuentes, E., Rojo-Martinez, G., Esteva, I., et al., (2005) Influence of age and sex on levels of anti-oxidized LDL antibodies and anti-LDL immune complexes in the general population, J. Lipid. Res., 46, 452?7.
[21] Canudas, J., Cenarro, A., Civeira, F., García-Otín, A. L., Arístegui, R., Díaz, C., et al., (2001) Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: Effect of the lipid-lowering agents, atorvastatin and bezafibrate, Metabolism, 50, 447?450.
[22] Brizzi, P., Tonolo, G., Bertrand, G., Carusillo, F., Severino, C., Maioli, M., et al., (2004) Autoantibodies against oxidized low-density lipoprotein (oxLDL) and LDL oxidation status, Clin. Chem. Lab. Med., 42, 164?70.
[23] Frosteg?rd, J., Tao, W., Georgiades, A., R?stam, L., Lindblad, U., and Lindeberg, S., (2007) Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea, Nutr Metab (Lond), 20, 7.
[24] Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A., et al., (2002) Innate and acquired immunity in atherogenesis, Nat. Med., 8, 1218–26.
[25] Palinski, W., Miller, E., Witztum, J. L., (1995) Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis, Proc. Natl. Acad. Sci., USA, 92, 821–5.
[26] Binder, C. J., H?rkk?, S., Dewan, A., Chang, M. K., Kieu, E. P., Goodyear, C. S., et al., (2003) Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL, Nat. Med., 9, 736–43.
[27] Ameli, S., Hultgardh-Nilsson, A., Regnstrom, J., Calara, F., Yano, J., Cercek, B., et al., (1996) Effect of immu- nization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits, Arteri-oscler Thromb Vasc Biol, 16, 1074–9.
[28] Pappalardo, F., Musumeci, S., and Motta, S., (2008) Modeling immune system control of atherogenesis, Bioinformatics.
[29] Orem, C., Orem, A., Uydu, H. A., Celik, S., Erdol, C., and Kural, B. V., (2002) The effects of lipid-lowering therapy on low-density lipoprotein auto-antibodies: Relationship with low-density lipoprotein oxidation and plasma total antioxidant status, Coron Artery Dis, 13, 65–71.
[30] Brizzi, P., Isaja, T., D'Agata, A., Malaguarnera, L., Malaguarnera, M., and Musumeci, S., (2002) Oxidized LDL antibodies (OLAB) in patients with beta thala- ssemia major, J. Atheroscler Thromb, 9, 139?44.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.