The effect of CpG-rich DNA fragments on the development of hypertension in spontaneously hypertensive rats (SHR)

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.