Nanostructure of Human Aortic Intima in Atherosclerosis (A Pilot Study)

Objective: to analyze the nanostructure of human aortic intima in atherosclerosis and demonstrate the poten tial effect of Niodex on cholesterol plaques.

Materials and methods. Samples of intima were taken from those parts of aorta, where different stages of atherosclerotic chages were obvious. Aortic samples were incubated in a solution containing cyclodextrins. A solution of NIODEX, a propylene glycol ester of betacyclodextrin, was used in the study. A layer of aortic intima was formed on the glass slide surface with polylysine. The samples were placed into the working area of an atomicforce microscope (Integra Prima, NTMDT, Russian Federation), and their surfaces were scanned. The number of imaging points was 512; and the imaging regions were as follows: 100100 μm, 20002000 nm.

Results. Classification of nanosurface objects was performed and typical fragments (craters, ridges, and trabecular fibers) were identified, and quantitative assessment of their sizes was carried out. 27 fragments were identified as growing cholesterol plaques. 16 of them measuring 900—1200 nm were identified near ridges, and 11 near craters (600—1050 nm). Niodex caused destruction of lipid spots and smoothing of the intima surface. More than a half of the 27 identified objects (15) demostrated a 30% and more decrease in size (median 340—400 nm). A 10—15% decrease was registered in 7 fragments; in the remaining 5 fragments, the decrease in the lesion size was less than 10%.

Conclusion. Raw data permit to suppose that the effect of Niodex on the aortic intima results in decceleartion and decreased intensity of atherosclerotic plaque growth on the intima fragments.

1. Dou Y., Guo J., Chen Y., Han S., Xu X., Shi Q., Jia Y., Liu Y., Deng Y., Wang R., Li X., Zhang J. Sustained delivery by a cyclodextrin material based nanocarrier potentiates antiatherosclerotic activity of rapamycin via selectively inhibiting mTORC1 in mice. J. Control. Release. 2016; 235: 48–62. http://dx.doi.org/10.1016/j.jconrel.2016.05.049. PMID: 27235978

2. Zimmer S., Grebe A., Bakke S.S., Bode N., Halvorsen B., Ulas T., Skjelland M., De Nardo D., Labzin L.I., Kerksiek A., Hempel C., Heneka M.T., Hawxhurst V., Fitzgerald M.L., Trebicka J., Björkhem I., Gustafsson J.Е., Westerterp M., Tall A.R., Wright S.D., Espevik T., Schultze J.L., Nickenig G., Lütjohann D., Latz E. Cyclodextrin promotes atherosclerosis regres sion via macrophage reprogramming. Sci. Transl. Med. 2016; 8 (333): 333ra50. http://dx.doi.org/10.1126/scitranslmed.aad6100. PMID:

3.

4. Wagner E.M., Jen K.L., Artiss J.D., Remaley A.T. Dietary alphacyclodextrin lowers lowdensity lipoprotein cholesterol and alters plasma fatty acid profile in lowdensity lipoprotein receptor knockout mice on a highfat diet. Metabolism. 2008; 57 (8): 1046–1051. http://dx.doi.org/10.1016/j.metabol.2008.02.020. PMID: 18640380

5. Kilsdonk E.P., Yancey P.G., Stoudt G.W., Bangerter F.W., Johnson W.J., Phillips M.C., Rothblat G.H. Cellular cholesterol efflux mediated by cyclodextrins. J. Biol. Chem. 1995; 270 (29): 17250–17256. http://dx.doi.org/10.1074/jbc.270.29.17250. PMID:7615524

6. Gens A.P., Ivanova A.G., Charchyan E.R., Stepanenko A.B. Gistomorfologicheskie osobennosti aorty i klapanov serdtsa pri sindrome Marfana i bolezni Erdgeima. [Histomorphological characteristics of aorta and heart valves in patients with Marfan syndrome and Erdheim disease]. Klinicheskaya i Eksperimentalnaya Khirurgiya. Zhurnal Imeni Akademika B.V. Petrovskogo. 2015; 2: 25–32. [In Russ.]

7. Kozlova E.K., Chernysh A.M., Moroz V.V., Kuzovlev A.N. Analysis of nanostructure of red blood cells membranes by space Fourier transform of AFM images. Micron. 2013; 44: 218–227. http://dx.doi.org/10.1016/j.micron.2012.06.012. PMID: 22854216

8. Moroz V.V., Chernysh A.M., Kozlova E.K., Borshegovskaya P.Y., Bliznjuk U.A., Rysaeva R.M., Gudkova O.E. Comparison of red blood cell mem brane microstructure after different physicochemical influences: atomic force microscope research. J. Crit. Care. 2010; 25 (3): 539.e1–539.e12.

9. Moroz V.V., Sergunova V.A., Nazarov B.F., Kozlova E.K., Chernysh A.M., Vlasov I.B. Izmeneniya nanostruktury membran krasnykh kletok krovi pri krovopotere na etapakh khirurgicheskogo lecheniya u bolnykh pri operatsiyakh na spinnom mozge. Obshchaya Reanimatologiya. [Changes in the nanostructure of red blood cells in intraoperative blood loss during spinal cord surgery. General Reanimatology]. 2013; 9 (2): 5–11. http://dx.doi.org/10.15360/18139779201325. [In Russ.]

10. Moroz V.V., Chernysh A.M., Kozlova E.K., Gudkova O.E., Sergunova V.A., Myagkova E.A., Kuzovlev A.N. Metodika mikroskopicheskogo analiza membran eritrotsitov. Obshchaya Reanimatologiya. [Procedure for microscopic analysis of red blood cell membranes. General Reanimatology]. 2013; 9 (5): 62–67. http://dx.doi.org/10.15360/181397792013562. [In Russ.]

11. Sergunova V.A., Kozlova E.K., Myagkova E.A., Chernysh A.M. Izmerenie uprugoelastichnykh svoistv membrany nativnykh eritrotsitov in vitro. Obshchaya Reanimatologiya. [In vitro measurement of the elastic properties of the native red blood cell membrane. General Reanimatology]. 2015; 11 (3): 39–44. http://dx.doi.org/10.15360/18139779201533944. [In Russ.]

12. Sergunova V.A., Gudkova O.E., Kozlov A.P., Chernysh A.M. Izmerenie lokalnoi zhestkosti membran eritrotsitov s pomoshchyu atomno silovoi spektroskopii. Obshchaya Reanimatologiya. [Measurement of the local tension of red blood cell membranes by atomic force spectroscopy. General Reanimatology]. 2013; 9 (1): 14–17. http://dx.doi.org/10.15360/181397792013114. [In Russ.]