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[血浆循环游离DNA及其所含高分子量富含CpG片段在动脉高血压和颈动脉闭塞性动脉粥样硬化发病机制中的血流动力学作用]

[Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

作者信息

Konorova I L, Veĭko N N, Ershova E S, Antelava A L, Chechetkin A O

出版信息

Angiol Sosud Khir. 2009;15(2):19-28.

PMID:19806935
Abstract

The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an increased content of rDNA, elevating as obliteration of the vessels' lumen increases, with the HR being decreased. The majority of them have degree II AH. In others, the pDNA concentration is by an order of magnitude higher than the normal values, while the rDNA content in pDNA is decreased, with the HR being elevated. Most of them have degree III AH. Pronounced and rough stenoses take an asymptomatic course in patients with decreased values of the HR and a slightly elevated level of pDNA and/or rDNA in the blood plasma. A higher level thereof leads to a rise in the HR and to the appearance of neurological symptomatology. Hence, CpG-DNA circulating in the composition of pDNA is a constantly acting endogenous blood factor decreasing the HR (the Toms's effect) and normalizing AP under physiological conditions, being however a cause of their increase and impairment of blood circulation in the pathogenesis of AH and atherosclerosis obliterans of the CAs.

摘要

血液的流体动力阻力(HR)是总外周阻力的组成部分之一。高分子量DNA似乎根据汤姆效应降低HR。本研究旨在调查对照供体、单纯患有动脉高血压(AH)或合并颈动脉(CA)动脉粥样硬化病变的患者血浆中循环的无细胞DNA(以下简称pDNA)的HR和特性。在pDNA的正常浓度范围内,我们发现HR与其以及富含高分子量CpG的部分(CpG-DNA),即核糖体重复序列(rDNA)的转录区域在pDNA中的含量呈负相关。所有检查患者中pDNA浓度的降低或升高均伴随着血浆中rDNA浓度的升高。超过一定水平似乎会导致HR和动脉血压(AP)升高。发现患有I级原发性AH的患者血浆的核酸内切酶活性降低,pDNA浓度高出两倍多,而rDNA含量无变化。他们的HR似乎升高(p<0.01)。诊断为II级AH的患者的特征是pDNA水平正常或降低,pDNA含量升高,HR略有降低。在患有ACs动脉粥样硬化闭塞症的患者中,颈动脉病变的初始表现通常在HR降低的背景下出现(p<0.05)。所有患有ACs动脉粥样硬化病变的患者可分为两组,我们认为这可能与动脉内膜破坏损伤的不同机制有关。其中一些患者的pDNA浓度与正常值无差异,但在其组成中,rDNA含量增加,随着血管腔闭塞增加而升高,HR降低。他们大多数患有II级AH。在其他患者中,pDNA浓度比正常值高一个数量级,而pDNA中的rDNA含量降低,HR升高。他们大多数患有III级AH。在HR值降低且血浆中pDNA和/或rDNA水平略有升高的患者中,明显且严重的狭窄呈无症状病程。其水平较高会导致HR升高并出现神经症状。因此,在pDNA组成中循环的CpG-DNA是一种持续起作用的内源性血液因子,在生理条件下降低HR(汤姆效应)并使AP正常化,但在AH和CAs动脉粥样硬化闭塞症的发病机制中是其升高和血液循环受损的原因。

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