Cor Vasa 2017, 59(2):e149-e156 | DOI: 10.1016/j.crvasa.2016.10.003
Circulating desialylated low density lipoprotein
- a Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia
- b Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow 121609, Russia
- c Department of Development and Regeneration, KU Leuven, Leuven, 3000 Belgium
- d Department of Cardiovascular Pathology, Russian Cardiology Research and Production Complex, Moscow 121552, Russia
Accumulation of lipids is the central event in the development of atherosclerotic lesion. Circulating low density lipoprotein (LDL) particles are known to be the major source of cholesterol and other lipids stored in atherosclerotic plaque. However, not all LDL particles possess atherogenic properties. In order to induce lipid accumulation in arterial cells, LDL particles have to undergo modifications. Although among such modifications the oxidation remains the most studied one, other atherogenic LDL modifications have been described. According to a series of studies conducted with blood serum and LDL from atherosclerotic patients, desialylation is one of the earliest if not the first atherogenic modification of LDL. Desialylation occurs in the bloodstream and is followed by a cascade of other modifications, including the reduction of LDL particle size and increase of its density, acquisition of negative electrical charge, oxidation and formation of highly atherogenic complexes. In this mini-review we will discuss the concept of multiple atherogenic modification of LDL leading to initiation and progression of atherosclerosis.
Keywords: Atherosclerosis; Low density lipoprotein; Modified LDL
Received: May 26, 2016; Revised: October 7, 2016; Accepted: October 13, 2016; Published: April 1, 2017 Show citation
References
- E. Matsuura, F. Atzeni, P. Sarzi-Puttini, et al., Is atherosclerosis an autoimmune disease?, BMC Medicine 12 (2014) 47.
Go to original source...
Go to PubMed...
- T. Reynolds, Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis, Journal of Clinical Pathology 66 (2013) 918-923.
Go to original source...
Go to PubMed...
- G. Nicolaou, C. Erridge, Toll-like receptor-dependent lipid body formation in macrophage foam cell formation, Current Opinion in Lipidology 21 (2010) 427-433.
Go to original source...
Go to PubMed...
- S.L. Stephen, K. Freestone, S. Dunn, et al., Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease, International Journal of Hypertension 2010 (2010) 646929.
Go to original source...
Go to PubMed...
- X.H. Yu, J. Zhang, X.L. Zheng, et al., Interferon-γ in foam cell formation and progression of atherosclerosis, Clinica Chimica Acta 441C (2015) 33-43.
Go to original source...
Go to PubMed...
- E. Uitz, B. Bahadori, M.F. McCarty, M.H. Moghadasian, Practical strategies for modulating foam cell formation and behavior, World Journal of Clinical Cases 2 (2014) 497-506.
Go to original source...
Go to PubMed...
- R.M. Chen, K. Fischer-Dzoga, Effect of hyperlipemic serum lipoproteins on the lipid accumulation and cholesterol flux of rabbit aortic medial cells, Atherosclerosis 28 (1977) 339-353.
Go to original source...
Go to PubMed...
- J.L. Goldstein, R.G. Anderson, M.S. Brown, Coated pits, coated vesicles, and receptor-mediated endocytosis, Nature 279 (1979) 679-685.
Go to original source...
Go to PubMed...
- A. Trpkovic, I. Resanovic, J. Stanimirovic, et al., Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases, Critical Reviews in Clinical Laboratory Sciences 52 (2015) 70-85.
Go to original source...
Go to PubMed...
- H. Arai, Oxidative modification of lipoproteins, Sub-Cellular Biochemistry 77 (2014) 103-114.
Go to original source...
Go to PubMed...
- D. Steinberg, J.L. Witztum, Oxidized low-density lipoprotein and atherosclerosis, Arteriosclerosis, Thrombosis, and Vascular Biology 30 (2010) 2311-2316.
Go to original source...
Go to PubMed...
- R.M. Krauss, Lipoprotein subfractions and cardiovascular disease risk, Current Opinion in Lipidology 21 (2010) 305-311.
Go to original source...
Go to PubMed...
- S. Hirayama, T. Miida, Small dense LDL: An emerging risk factor for cardiovascular disease, Clinica Chimica Acta 414 (2012) 215-224.
Go to original source...
Go to PubMed...
- H.F. Hoff, J.W. Gaubatz, Isolation, purification, and characterization of a lipoprotein containing Apo B from the human aorta, Atherosclerosis 42 (1982) 273-297.
Go to original source...
Go to PubMed...
- P. Avogaro, G.B. Bon, G. Cazzolato, Presence of a modified low density lipoprotein in humans, Arteriosclerosis 8 (1988) 79-87.
Go to original source...
- L.Y. Ke, N. Stancel, H. Bair, C.H. Chen, The underlying chemistry of electronegative LDL's atherogenicity, Current Atherosclerosis Reports 16 (2014) 428.
Go to original source...
Go to PubMed...
- A.P. Mello, I.T. da Silva, D.S. Abdalla, N.R. Damasceno, Electronegative low-density lipoprotein: origin and impact on health and disease, Atherosclerosis 215 (2011) 257-265.
Go to original source...
Go to PubMed...
- J.L. Sánchez-Quesada, S. Villegas, J. Ordóñez-Llanos, Electronegative low-density lipoprotein. A link between apolipoprotein B misfolding, lipoprotein aggregation and proteoglycan binding, Current Opinion in Lipidology 23 (2012) 479-486.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, I.D. Novikov, et al., Lipids in cells of atherosclerotic and uninvolved human aorta. I. Lipid composition of aortic tissue and enzyme-isolated and cultured cells, Experimental and Molecular Pathology 42 (1985) 117-137.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, S.N. Pokrovsky, et al., Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination, Circulation Research 62 (1988) 421-429.
Go to original source...
Go to PubMed...
- V.V. Tertov, A.N. Orekhov, O.N. Martsenyuk, et al., Low-density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells, Experimental and Molecular Pathology 50 (1989) 337-347.
Go to original source...
Go to PubMed...
- E.I. Chazov, V.V. Tertov, A.N. Orekhov, et al., Atherogenicity of blood serum from patients with coronary heart disease, Lancet 2 (1986) 595-598.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, D.N. Mukhin, Desialylated low density lipoprotein - naturally occurring modified lipoprotein with atherogenic potency, Atherosclerosis 86 (1991) 153.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, D.N. Mukhin, I.A. Mikhailenko, Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients, Biochemical and Biophysical Research Communications 162 (1989) 206-211.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, A.G. Tonevitsky, et al., Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography, Biochemical and Biophysical Research Communications 167 (1990) 1122-1127.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, Z.A. Gabbasov, et al., Multiple-modified desialylated low density lipoproteins that cause intracellular lipid accumulation. Isolation, fractionation and characterization, Laboratory Investigation 67 (1992) 665-675.
Go to PubMed...
- V.V. Tertov, A.N. Orekhov, Metabolism of native and naturally occurring multiple modified low density lipoprotein in smooth muscle cells of human aortic intima, Experimental and Molecular Pathology 64 (1997) 127-145.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, S.A. Kudryashov, V.N. Smirnov, Triggerlike stimulation of cholesterol accumulation and DNA and extracellular matrix synthesis induced by atherogenic serum or low density lipoprotein in cultured cells, Circulation Research 66 (1990) 311-320.
Go to original source...
Go to PubMed...
- V.V. Tertov, A.N. Orekhov, L.H. Ryong, V.N. Smirnov, Intracellular cholesterol accumulation is accompanied by enhanced proliferative activity of human aortic intimal cells, Tissue and Cell 20 (1988) 849-854.
Go to original source...
Go to PubMed...
- V.V. Tertov, V.V. Kaplun, S.N. Dvoryantsev, A.N. Orekhov, Apolipoprotein B-bound lipids as a marker for evaluation of low density lipoprotein oxidation in vivo, Biochemical and Biophysical Research Communications 214 (1995) 608-613.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, V.V. Kaplun, A.N. Orekhov, Antioxidant content in low density lipoprotein and lipoprotein oxidation in vivo and in vitro, Free Radical Research 29 (1998) 165-173.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, A.E. Kabakov, et al., Autoantibodies against modified low density lipoprotein. Nonlipid factor of blood plasma that stimulates foam cell formation, Arteriosclerosis and Thrombosis 11 (1991) 316-326.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, A.N. Orekhov, Characterization of desialylated low-density lipoproteins which cause intracellular lipid accumulation, International Journal of Tissue Reactions 14 (1992) 155-162.
Go to PubMed...
- V.V. Tertov, G. Bittolo-Bon, I.A. Sobenin, et al., Naturally occurring modified low density lipoproteins are similar if not identical: more electronegative and desialylated lipoprotein subfractions, Experimental and Molecular Pathology 62 (1995) 166-172.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, A.N. Orekhov, Similarity between naturally occurring modified desialylated, electronegative and aortic low density lipoprotein, Free Radical Research 25 (1996) 313-319.
Go to original source...
Go to PubMed...
- M. La Belle, R.M. Krauss, Differences in carbohydrate content of low density lipoproteins associated with low density lipoprotein subclass patterns, Journal of Lipid Research 31 (1990) 1577-1588.
Go to original source...
Go to PubMed...
- V.V. Tertov, V.V. Kaplun, I.A. Sobenin, A.N. Orekhov, Low-density lipoprotein modification occurring in human plasma possible mechanism of in vivo lipoprotein desialylation as a primary step of atherogenic modification, Atherosclerosis 138 (1998) 183-195.
Go to original source...
Go to PubMed...
- V.V. Tertov, V.V. Kaplun, I.A. Sobenin, et al., Human plasma trans-sialidase causes atherogenic modification of low density lipoprotein, Atherosclerosis 159 (2001) 103-115.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, D.N. Mukhin, et al., Association of low-density lipoprotein with particulate connective tissue matrix components enhances cholesterol accumulation in cultured subendothelial cells of human aorta, Biochimica et Biophysica Acta 928 (1987) 251-258.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, D.N. Mukhin, et al., Insolubilization of low density lipoprotein induces cholesterol accumulation in cultured subendothelial cells of human aorta, Atherosclerosis 79 (1989) 59-70.
Go to original source...
Go to PubMed...
- I.A. Sobenin, I.V. Suprun, V.P. Karagodin, et al., The interaction of plasma sialylated and desialylated lipoproteins with collagen from the intima and media of uninvolved and atherosclerotic human aorta, Journal of Lipids 2011 (2011) 254267.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, Z.A. Gabbasov, et al., Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation in human aortic intimal cells - the role of lipoprotein aggregation, European Journal of Clinical Chemistry and Clinical Biochemistry 30 (1992) 300-308.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, Z.A. Gabbasov, et al., Lipoprotein aggregation as an essential condition of intracellular lipid accumulation caused by modified low density lipoproteins, Biochemical and Biophysical Research Communications 163 (1989) 489-494.
Go to original source...
Go to PubMed...
- V.V. Tertov, A.N. Orekhov, I.A. Sobenin, et al., Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation due to lipoprotein aggregation, Circulation Research 71 (1992) 218-228.
Go to original source...
Go to PubMed...
- O.M. Panasenko, I.V. Suprun, A.A. Melnichenko, et al., Low ionic strength promotes association of circulating modified LDL in human blood, Bulletin of Experimental Biology and Medicine 138 (2004) 248-250.
Go to original source...
Go to PubMed...
- O.M. Panasenko, D.V. Aksenov, A.A. Melnichenko, et al., Proteolysis of apoprotein B-100 impairs its topography on LDL surface and reduces LDL association resistance, Bulletin of Experimental Biology and Medicine 140 (2005) 521-525.
Go to original source...
Go to PubMed...
- D.V. Aksenov, A.A. Melnichenko, I.V. Suprun, et al., Phospholipid hydrolysis with phospholipases A2 and C impairs apolipoprotein B-100 conformation on the surface of low density lipoproteins by reducing their association resistance, Bulletin of Experimental Biology and Medicine 140 (2005) 419-422.
Go to original source...
Go to PubMed...
- A.A. Melnichenko, V.V. Tertov, O.A. Ivanova, et al., Desialylation decreases the resistance of apo B-containing lipoproteins to aggregation and increases their atherogenic potential, Bulletin of Experimental Biology and Medicine 140 (2005) 51-54.
Go to original source...
Go to PubMed...
- I.V. Suprun, A.A. Melnichenko, I.A. Sobenin, et al., Resistance of native and circulating modified low-density lipoproteins in human blood to association, Bulletin of Experimental Biology and Medicine 138 (2004) 380-383.
Go to original source...
- A.A. Melnichenko, D.V. Aksenov, O.M. Panasenko, et al., Pluronics suppress association of low-density lipoproteins inducing atherogenesis, Bulletin of Experimental Biology and Medicine 156 (2014) 631-634.
Go to original source...
Go to PubMed...
- I.G. Panova, V.V. Spiridonov, I.B. Kaplan, et al., Inhibitory effect of polyethylene oxide and polypropylene oxide triblock copolymers on aggregation and fusion of atherogenic low density lipoproteins, Biochemistry (Moscow) 80 (2015) 1057-1064.
Go to original source...
Go to PubMed...
- A.A. Melnichenko, D.V. Aksenov, V.A. Myasoedova, et al., Pluronic block copolymers inhibit low density lipoprotein self-association, Lipids 47 (2012) 995-1000.
Go to original source...
Go to PubMed...
- A.N. Orekhov, V.V. Tertov, A.E. Kabakov, et al., Autoantibodies against modified low density lipoprotein. Nonlipid factor of blood plasma that stimulates foam cell formation, Arteriosclerosis and Thrombosis 11 (1991) 316-326.
Go to original source...
Go to PubMed...
- I.A. Sobenin, J.T. Salonen, A.V. Zhelankin, et al., Low density lipoprotein-containing circulating immune complexes: role in atherosclerosis and diagnostic value, BioMed Research International 2014 (2014) 205697.
Go to original source...
Go to PubMed...
- I.A. Sobenin, V.P. Karagodin, A.C. Melnichenko, et al., Diagnostic and prognostic value of low density lipoprotein-containing circulating immune complexes in atherosclerosis, Journal of Clinical Immunology 33 (2013) 489-495.
Go to original source...
Go to PubMed...
- V.V. Tertov, I.A. Sobenin, A.N. Orekhov, et al., Characteristics of low density lipoprotein isolated from circulating immune complexes, Atherosclerosis 122 (1996) 191-199.
Go to original source...
Go to PubMed...
- A.G. Kacharava, V.V. Tertov, A.N. Orekhov, Autoantibodies against low-density lipoprotein and atherogenic potential of blood, Annals of Medicine 25 (1993) 551-555.
Go to original source...
Go to PubMed...
- A.N. Orekhov, O.S. Kalenich, V.V. Tertov, I.D. Novikov, Lipoprotein immune complexes as markers of atherosclerosis, International Journal of Tissue Reactions 13 (1991) 233-236.
Go to PubMed...
- A.N. Orekhov, Y.V. Bobryshev, I.A. Sobenin, et al., Modified low density lipoprotein and lipoprotein-containing circulating immune complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1 diabetes macrovascular disease, International Journal of Molecular Sciences 15 (2014) 12807-12841.
Go to original source...
Go to PubMed...
- I.A. Sobenin, V.A. Myasoedova, A.A. Melnichenko, et al., The method of diagnostics of predisposition to the development of atherosclerosis. Patent application RU 2014150315 A of December 12, 2014, Inventions Utility Models: The Official Bulletin of Federal Service for Intellectual Property (Pospatent) 19 (2016, July).
- V.V. Tertov, I.A. Sobenin, A.N. Orekhov, Modified (desialylated) low-density lipoprotein measured in serum by lectin-sorbent assay, Clinical Chemistry 41 (1995) 1018-1021.
Go to original source...
- P.T. Williams, X.Q. Zhao, S.M. Marcovina, et al., Levels of cholesterol in small LDL particles predict atherosclerosis progression and incident CHD in the HDL-atherosclerosis treatment study (HATS), PLoS ONE 8 (2013) e56782.
Go to original source...
Go to PubMed...
- T. Yamazaki, R. Nohara, H. Daida, et al., Intensive lipid-lowering therapy for slowing progression as well as inducing regression of atherosclerosis in Japanese patients: subanalysis of the JART study, International Heart Journal 54 (2013) 33-39.
Go to original source...
Go to PubMed...
- R. Bambauer, C.J. Olbricht, E. Schoeppe, Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results, Therapeutic Apheresis 1 (1997) 242-248.
Go to original source...
Go to PubMed...
- A.N. Orekhov, A.A. Melnichenko, I.A. Sobenin, Approach to reduction of blood atherogenicity, Oxidative Medicine and Cellular Longevity 2014 (2014) 738679.
Go to original source...
Go to PubMed...
- A.N. Orekhov, Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention, Current Pharmaceutical Design 19 (2013) 5909-5928.
Go to original source...
Go to PubMed...
- A.N. Orekhov, E.A. Ivanova, Cellular models of atherosclerosis and their implication for testing natural substances with anti-atherosclerotic potential, Phytomedicine 23 (2016) 1190-1197.
Go to original source...
Go to PubMed...
- A.N. Orekhov, I.A. Sobenin, V.V. Revin, Y.V. Bobryshev, Development of antiatherosclerotic drugs on the basis of natural products using cell model approach, Oxidative Medicine and Cellular Longevity 2015 (2015) 463797.
Go to original source...
Go to PubMed...
- A.N. Orekhov, I.A. Sobenin, N.V. Korneev, et al., Anti-atherosclerotic therapy based on botanicals, Recent Patents on Cardiovascular Drug Discovery 8 (2013) 56-66.
Go to original source...
Go to PubMed...
- V.A. Myasoedova, T.V. Kirichenko, A.A. Melnichenko, et al., Anti-atherosclerotic effects of a phytoestrogen-rich herbal preparation in postmenopausal women, International Journal of Molecular Sciences 17 (2016). pii:E1318.
Go to original source...
Go to PubMed...
- T.V. Kirichenko, I.A. Sobenin, D. Nikolic, et al., Anti-cytokine therapy for prevention of atherosclerosis, Phytomedicine 23 (2016) 1198-1210.
Go to original source...
Go to PubMed...
- I.A. Sobenin, V.A. Myasoedova, A.N. Orekhov, Phytoestrogen-rich dietary supplements in anti-atherosclerotic therapy in postmenopausal women, Current Pharmaceutical Design 22 (2016) 152-163.
Go to original source...
Go to PubMed...