Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates.
Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates.
复制标题
血小板衍生的多磷酸二腺苷诱导血液透析患者血管生长增加。
DOI：
10.1046/j.1523-1755.2001.0590031134.x
复制
发表时间：
2001
影响因子：
19.6
通讯作者：
Martin Tepel
中科院分区：
文献类型：
--
作者：
J. Jankowski;J. Hagemann;M. Yoon;M. van der Giet;N. Stephan;W. Zidek;H. Schlüter;Martin Tepel
背景
血管平滑肌细胞（VSMC）生长增强是动脉粥样硬化的标志之一。负责刺激动脉平滑肌细胞生长的一种机制是从聚集在内皮损伤处的血小板释放生长因子。由于在终末期肾功能衰竭（ESRF）动脉粥样硬化形成显着加速，VSMC生长因子的释放对血小板聚集血液透析患者，ESRF患者在透析前阶段，和健康受试者进行了检查。
方法
凝血酶激活血小板，并测试上清液对大鼠主动脉VSMCs的生长刺激。用[3 H]-胸苷掺入法测定细胞增殖率。使用基于亲和色谱法和反相色谱法建立的色谱测定法测定上清液和完整血小板中的二腺苷多磷酸（Ap（n）A，N = 3至6）含量。
结果
与健康对照受试者的上清液相比，来自血液透析患者（N = 15）的凝血酶活化的血小板上清液增加VSMC中[（3）H]-胸苷掺入率（N = 17，10（6）个刺激的血小板的计数/上清液+/- SEM，604 +/- 71 vs. 364 +/- 45，P < 0.05）。向上清液中加入选择性P2受体阻断剂磷酸吡哆醛-6-偶氮苯基-2，4-二磺酸可抑制Ap（n）A对血管平滑肌细胞生长的刺激作用（219 +/- 53对156 +/- 71计数/106个刺激血小板的上清液+/- SEM）。Ap（n）A（N = 3至6）血液透析患者的凝血酶活化血小板上清液的量显著高于10名健康对照受试者的血小板（Ap（3）A，119 +/- 32 vs. 12 +/- 3; Ap（4）A，154 +/- 59 vs. 43 +/- 20; Ap（5）A，39 +/- 14 vs. 13 +/- 6; Ap（6）A，42 +/- 19 vs. 2 +/- 1 fg/血小板+/- SEM，各P < 0.05，N = 10）。细胞内Ap（n）A血液透析患者（N = 61）的完整血小板数量（N = 3 ~ 6）显著高于健康对照组[N = 30，A p（n）A数量（fg/血小板+/- SEM）：Ap（3）A，366 +/- 68 vs. 14.7 +/- 1; Ap（4）A，336 +/- 48 vs. 19 +/- 2; Ap（5）A，227 +/- 35 vs. 10 +/- 1; Ap（6）A，141 +/- 45 vs. 4 +/- 1;各P < 0.01]。
结论
血液透析患者血小板中多磷酸二核苷含量的增加可能是一个重要的致动脉粥样硬化因素。
BACKGROUND
Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined.
METHODS
Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods.
RESULTS
The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01].
CONCLUSIONS
The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.
水溶性碳二亚胺对腺苷-5-聚磷酸的作用。
影响因子：
14.9
作者：
Ng,KE;Orgel,LE
通讯作者：
Orgel,LE
影响因子：
158.5
作者：
Rosamond, WD;Chambless, LE;Heiss, G
通讯作者：
Heiss, G