Abstract
In this study we have investigated properties of blood plasma extracellular DNA (cell-free DNA, cfDNA) from patients with essential arterial hypertension (AH). Concentration of cell-free DNA was basically the same as in healthy donors, however, the content of the marker, CpG-rich cell-free DNA fragments (CpG-DNA) of the transcribed area of the ribosomal repeat (TArDNA, CpG-DNA) was higher in AH patients. For evaluation of the effect of CpG-DNA on the development of arterial hypertension 2-day-old SHR rat pups and corresponding controls of normotensive WKY rats received a single subcutaneous injection of human TArDNA (700 ng) to generate anti-CpG-DNA antibodies (and thus to alter the CpG-DNA content in total cfDNA). After 9 weeks blood pressure (BP) in SHR rats immunized with CpG-DNA was significantly lower than in control SHR rats and was basically the same as in WKY rats. However, subsequently, BP of the immunized SHR exhibited age-related increase, which reached the stably high values typical for mature SHR 8 weeks later compared with control SHR. Analysis of cfDNA has shown that in 17-week-old immunized SHR rats concentrations of cell-free DNA and its small DNA fragments are lower and the content of CpG-DNA (rat TArDNA) is higher than in corresponding controls. These changes were accompanied by a 3.5-fold increase in blood endonuclease activity and the decrease in content of free (unbound to cfDNA) anti-CpG-DNA antibodies. Total content of anti-CpG-DNA antibodies in the immunized rats was the same as in control animals. Thus, the delayed age-related increase in stable BP observed in immunized SHR rats is obviously not associated with increased generation of anti-CpG-DNA antibodies. Possible reasons of this effect are discussed.
Similar content being viewed by others
References
Gogin, E.E. and Gogin, G.E., Gipertonicheskaya bolezn’ i assotsiirovannye bolezni sistemy krovoobrashcheniya (Hypertonic Diseases and Associated Diseases of the Blood Circulation System), Moscow: Newdiamed.
Veiko, N.N., Bulycheva, N.V., Roginko, O.A., Veiko, R.V., Ershova, E.S., Kozdoba, O.A., Kuz’min, V.A., Vinogradov, A.M., Iudin, A.A., and Speranskii, A.I., Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2008, vol. 2, pp. 198–207.
Ae-Kyung, Yi., Tuetken, R., Redford, T., MaWaldschmid, R., Kirsch, J., and Krieg, A., J. Immunology, 1998, vol. 160, pp. 4755–4761.
Klinman, D., Ylt, A., Beaucage, S., Conover, J., and Krieg, A., Immunology, 1996, vol. 93, pp. 2879–2883.
Fitzner, N., Clauberg, S., Essmann, F., Liebmann, J., and Kolb-Bachofen, V., Clin. Vaccine Immunol., 2008, vol. 15, pp. 138–146.
Gannushkina, I.V., in Ocherki angionevrologii (Essays in Angioneurology), Suslina, Z.A., Ed., Moscow: Atmosphera, 2005, pp. 17–40.
Gannushkina, I.V. and Konorova, I.L., Patol. Fiziol. Eksper. Ter., 2008, no. 3, pp. 2–10.
Veiko, N.N. and Spitkovskii, D.M. Radiatsionnaya Biologiya. Radioekologiya, 2000, vol. 40, pp. 396–404.
Gannushkina, I.V., Antelava, A.L., and Veiko, N.N., Patol. Fiziol. Eksper. Ter., 2000, no. 4, pp. 3–5.
Gannushkina, I.V., Farago, M.L., Antelava, A.L., Baranchikova, M.V., and Veiko, N.N., Vestnik RAMN, 1998, vol. 5(14), pp. 16–22.
Cho, H., Bae, Y., and Jung, J., Stem. Cells, 2006, vol. 24, pp. 2744–2752.
Sambrook, J., Fritsch, E., and Maniatis, T., Molecular Cloning: A Laboratory Manual, 2nd Edn., NY: Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989.
Aida, Y. and Pabst, M., Immunol. Methods, 1990, vol. 132, pp. 191.
Veiko, N.N., Egolina, N.A., Radzivil, G.G., Nurbaev, S.D., Kosyakova, N.V., Shubaeva, N.O., and Lyapunova, N.A., Mol. Biol., 2003, vol. 37, pp. 409–419.
Ermakov, A.V., Kostyuk, S.V., Egolina, N.A., Kalashnikova, E.A., Kokarovtseva, S.N., Malinovskaya, E.M., and Veiko, N.N., Radiatsionnaya Biologiya. Radioekologiya, 2007, vol. 47, pp. 133–140.
Veiko, N.N., Kostyuk, S.V., Ermakov, A.V., Kalashnikova, E.A., Ryazantseva, T.A., and Speranskii, A.I., Byull. Eksper. Biol. Med., 2007, vol. 144, pp. 304–308.
Veiko, N.N., Shubaeva, N.O., Ivanova, S.M., Speranskii, A.I., Lyapunova, N.A., and Spitkovskii, D.M., Byull. Eksper. Biol. Med., 2006, vol. 143, pp. 313–316.
Neverova, M.E., Fidelina, O.V., Mkrtumova, N.A., Postnov, A.Yu., Postnova, D.A., and Kalinin, V.N., Kardiologiya, 2008, vol. 48, pp. 41–45.
Shiokawa, D., Shika, Y., Saito, K., Yamazaki, K., and Tanuma, S., Biochem J., 2005, vol. 392, pp. 511–517.
Sharifi, A. and Schiffrin, E., Am. J. Hypertens, 1998, vol. 11, pp. 1108–1116.
Hamlet, P., Richard, L., Dam, T.V., Teiger, E., Orlov, S.N., Gaboury, L., Gossard, F., and Themblay, J., Hypertension, 1995, vol. 26, pp. 642–648.
Sanjuan, M., Rao, N., Lai, K-T., Gu, Y., Sun, S., Fuchs, A., Fung-Leung, W-P., Colonna, M., and Karlsson, L., J. Cell Biol., 2006, vol. 172, pp. 1057–1068.
Ashman, R., Goeken, J., Drahos, J., and Lenert, P., Int. Immunol., 2005, vol. 17, pp. 411–420.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © N.N. Veiko, I.L. Konorova, M.E. Neverova, O.V. Fidelina, N.A. Mkrtumova, E.S. Ershova, M.S. Kon’kova, A.Yu. Postnov, 2010, published in Biomeditsinskaya Khimiya.
Rights and permissions
About this article
Cite this article
Veiko, N.N., Konorova, I.L., Neverova, M.E. et al. The effect of CpG-rich DNA fragments on the development of hypertension in spontaneously hypertensive rats (SHR). Biochem. Moscow Suppl. Ser. B 4, 269–278 (2010). https://doi.org/10.1134/S1990750810030091
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990750810030091