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Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment

Abstract:

The large research series has become internationally known in the 1980s and continues until today. Cultures of cultured or incubated smooth muscle cells or monocytes/macrophages were used for the measurement of capacities of substances to enhance or lower intracellular cholesterol deposition, which was interpreted as anti-or pro-atherogenic action. The LDL from patients with coronary atherosclerosis caused a 2-4 times elevation of cholesterol contents within the cultured cells. Incubation with sera or LDL from healthy subjects did not induce cholesterol accumulation. Various drugs and natural substances were found to possess pro-or anti-atherogenic potencies. Anti-atherogenic effect of different preparations of plant origin was reported: if an agent induced intracellular lipid accumulation it was regarded atherogenic and vice versa. However, if a pharmacological agent lowers the uptake of lipids by cells in a culture, it should be expected to increase the blood cholesterol level in vivo. It can be reasonably assumed that a drug, inhibiting cholesterol uptake by cultured cells, would elevate the blood cholesterol level in vivo. By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in sites with damaged endothelial barrier and vulnerable plaques. The agents supposedly having an anti-atherogenic potency in a cell culture might reduce cholesterol uptake diffusely by entire cell populations contributing thereby to hypercholesterolemia. On the contrary, atherosclerosis is a focal disease, affecting primarily damaged sites of the vascular lining, which would be favored by hypercholesterolemia.

Info:

Periodical:

International Journal of Pharmacology, Phytochemistry and Ethnomedicine (Volume 1)

Pages:

10-14

DOI:

https://doi.org/10.18052/www.scipress.com/IJPPE.1.10

Citation:

S. Jargin "Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment", International Journal of Pharmacology, Phytochemistry and Ethnomedicine, Vol. 1, pp. 10-14, 2015

Online since:

Dec 2015

Authors:

Sergei Jargin

Keywords:

Atherosclerosis, Cell Culture, Dietary Supplements

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Open Access

This work is licensed under a
Creative Commons Attribution 4.0 International License

References:

34. A.N. Orekhov, E.M. Pivovarova, I.A. Sobenin, V.V. Yakushkin and V.V. Tertov, Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil, Drugs 44 Suppl 1 (1992) 105-110.

A.N. Orekhov, Direct anti-atherosclerotic therapy; development of natural antiatherosclerotic drugs preventing cellular cholesterol retention, " Curr. Pharm. Des. 19 (2013) 5909-5928.

I.A. Sobenin, D.A. Chistiakov, Y.V. Bobryshev and A.N. Orekhov, Blood atherogenicity as a target for anti-atherosclerotic therapy, Curr. Pharm. Des. 19 (2013) 5954-5962.

A.N. Orekhov, I.A. Sobenin, V.V. Revin and Y.V. Bobryshev, Development of antiatherosclerotic drugs on the basis of natural products using cell model approach, Oxid. Med. Cell Longev. 2015 (2015) 463797.

T.A. Shchelkunova, I.A. Morozov, P.M. Rubtsov, L.M. Samokhodskaya, I.V. Andrianova, E.G. Rudimov, I.A. Sobenin, A.N. Orekhov, A.N. Smirnov, Effect of sex hormones on levels of mRNAs coding for proteins involved in lipid metabolism in macrophages, Biochem (Mosc) 78 (2013).

A.N. Orekhov, V V. Tertov, S.N. Pokrovsky, I. Yu. Adamova, O.N. Martsenyuk, A.A. Lyakishev, V.N. Smirnov, Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of lowdensity lipoproteins and an approach to its elimination, Circ Res. 62 (1988).

V.V. Tertov, A.N. Orekhov, I.A. Sobenin, Z.A. Gabbasov, E.G. Popov, A.A. Yaroslavov, V.N. Smirnov, Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation due to lipoprotein aggregation, Circ Res. 71 (1992).

D. Aksenov, D. Orekhova, R. Kireev, I. Andrianova, A. Smirnov, I. Sobenin, O. Panasenko, Effects of sex hormones on intracellular cholesterol accumulation and LDL aggregation, Abstracts of the 77th Congress of the European Atherosclerosis Society, 26-29 April 2008, Istanbul. Atheroscler Suppl. 9 (2008).

R.A. Kireev, E. Kuvshinova, I.V. Andrianova, I.A. Sobenin and A.N. Orekhov, Effect of sex hormones on atherosclerotic indices in primary culture of female cells, Abstracts of the 14th International Symposium on Atherosclerosis, 18-22 June 2006, Rome. Atheroscler Suppl. 7 (2006).

N.A. Nikitina, I.A. Sobenin, V.A. Myasoedova, VV Korennaya, AA Mel'nichenko, EM Khalilov, AN. Orekhov, Antiatherogenic effect of grape flavonoids in an ex vivo model, Bull Exp Biol Med 141 (2006) 712-715.

A.N. Orekhov, I.A. Sobenin, N.V. Korneev, T.V. Kirichenko, V.A. Myasoedova, A.A. Melnichenko, M. Balcells, E.R. Edelman, Y.V. Bobryshev, Anti-atherosclerotic therapy based on botanicals, Recent. Pat. Cardiovasc. Drug Discov. 8 (2013) 56-66.

L.H. Ryong, V.V. Tertov, A.V. Vasil'ev, V.A. Tutel'yan, and A.N. Orekhov, Antiatherogenic and antiatherosclerotic effects of mushroom extracts revealed in human aortic intima cell culture, Drug Dev. Res. 17 (1989) 109-117.

A.N. Orekhov, G.N. Baldenkov, V.V. Tertov, L.H. Ryong, S.G. Kozlov, A.A. Lyakishev, V.A. Tkachuk, M. Ya. Ruda, V.N. Smirnov, Cardiovascular drugs and atherosclerosis: Effects of calcium antagonists, betablockers, and nitrates on atherosclerotic characteristics of human aortic cells, J. Cardiovasc. Pharmacol. 12 Suppl 6 (1988).

S.V. Jargin, Cell Culture as a Testing System for Anti-Atherogenic Substances: A Brief Communication, Acta Pharm. Sci. 50 (2008) 237-240.

S.V. Jargin, Testing of serum atherogenicity on cell cultures: assessment of reliability, Gazz. Med. Ital. 170 (2011) 159-163.

S.V. Jargin, Testing of serum atherogenicity in cell cultures: questionable data published, Ger Med Sci. 10 (2012) Doc02.

S.V. Jargin, Orekhov's Method: Reassessment of in vitro lipid uptake assays, Recent Pat Cardiovasc Drug Discov. 9 (2015) 122-125.

A. Vogt, The genetics of familial hypercholesterolemia and emerging therapies, Appl Clin Genet. 8 (2015) 27-36.

J.L. Goldstein and M.S. Brown, The LDL receptor, Arterioscler Thromb Vasc Biol. 29 (2009) 431-438.

J.L. Goldstein and M.S. Brown, Progress in understanding the LDL receptor and HMG-CoA reductase, two membrane proteins that regulate the plasma cholesterol, J. Lipid Res. 25 (1984) 1450-1461.

R. Ricciarelli, J.M. Zingg and A. Azzi, Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells, Circulation. 102 (2000) 82-87.

V. Llorente-Cortés and L. Badimon, LDL receptor-related protein and the vascular wall: implications for atherothrombosis, Arterioscler. Thromb. Vasc. Biol. 25 (2005) 497-504.

Q. Gong and R.E. Pitas, Synergistic effects of growth factors on the regulation of smooth muscle cell scavenger receptor activity, J. Biol. Chem. 270 (1995) 21672-21678.

A. Pirillo, G.D. Norata and A.L. Catapano, LOX-1, OxLDL, and atherosclerosis, Mediators Inflamm. 2013 (2013) 152786.

S. Xu, S. Ogura, J. Chen, P.J. Little, J. Moss, and P. Liu, LOX-1 in atherosclerosis: biological functions and pharmacological modifiers, Cell Mol. Life Sci. 70 (2013) 2859-2872.

I.A. Sobenin, I.V. Andrianova, O.N. Demidova, T. Gorchakova, and A.N. Orekhov, Lipidlowering effects of time-released garlic powder tablets in double-blinded placebo-controlled randomized study, J. Atheroscler. Thromb. 15 (2008) 334-338.

H.K. Berthold and T. Sudhop, Garlic preparations for prevention of atherosclerosis, Curr. Opin. Lipidol. 9 (1998) 565-569.

M.H. Pittler and E. Ernst, Clinical effectiveness of garlic (Allium sativum), Mol. Nutr. Food Res. 51 (2007) 1382-1385.

M. Mahdavi-Roshan, A. Zahedmehr, A. Mohammad-Zadeh, HR Sanati, F Shakerian, A Firouzi, R Kiani, J. Nasrollahzadeh, Effect of garlic powder tablet on carotid intima-media thickness in patients with coronary artery disease: a preliminary randomized controlled trial, Nutr. Health. 22 (2013).

A.L. Vertkin, E.D. Li, I.A. Pyshkina and A.N. Orekhov, Role of fish food additives in the treatment and prophylaxis of atherogenic dyslipidemia, Kardiologiia 34 (1994) 22-28.

I. A. Sobenin, Principles of pathogenetic therapy of atherosclerosis. Dissertation, Research Institute for Pathology and Pathophysiology, Moscow, 2006. (Russian).

E.M. Pivovarova, Treatment of atherosclerosis, in: A.V. Pokrovsky (Ed. ), Clinical angiology, Moscow: Meditsina, vol. 2, p.2004) 712-714. (Russian).

S. Gorinstein, Z. Jastrzebski, J. Namiesnik, H. Leontowicz, M. Leontowicz and S. Trakhtenberg, The atherosclerotic heart disease and protecting properties of garlic: contemporary data, Mol. Nutr. Food Res. 51 (2007) 1365-1381.

M. Schneider, B. Loretz, M. Windbergs, N. Schneider-Daum, U.F. Schaefer and C. -M. Lehr, Biological barriers - Advanced drug delivery, in vitro modelling, and their implications for infection research, Eur. J. Pharm. Biopharm. 95 Pt A (2015) 1-2.

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