In vitro platelet responsiveness to adenosine-mediated "preconditioning" is age-dependent.
In vitro platelet responsiveness to adenosine-mediated "preconditioning" is age-dependent.
复制标题
体外血小板对腺苷介导的“预处理”的反应是年龄依赖性的。
DOI：
10.1007/s11239-005-0849-0
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发表时间：
2005
影响因子：
4
通讯作者：
Whittaker,Peter
中科院分区：
文献类型：
--
作者：
Przyklenk,Karin;Whittaker,Peter
背景资料：短暂的预处理（PC）缺血，除了其良好的心脏保护作用，已被证明在一些研究中，作用于循环血小板和减弱血小板粘附和聚集在不稳定型心绞痛和急性心肌梗死模型。PC的这种“抗血小板”作用可能是通过缺血/再灌注心肌腺苷的释放和血小板表面腺苷A2受体的激活而触发的。然而：（1）目前关于PC缺血和A2受体刺激的血小板抑制作用的所有数据都是在成年人群中获得的;（2）有证据表明心肌腺苷释放、受体反应性和受体后信号传导存在年龄相关的改变。我们的目的是使用一个已建立的体外血小板聚集模型和外源性给予腺苷A2激动剂，老年人群中腺苷A2受体刺激对血小板反应性的有利影响是否会受到损害。方法：从年轻成年兔与老年兔（6个月与4岁）以及年轻成年大鼠与衰老大鼠（4个月与2岁）中获取动脉血样本。年龄）。将每只动物的匹配等分试样随机分配接受A2激动剂CGS 21680或溶剂的外源性处理。全血阻抗aggregometry，使用胶原作为aggregatory stimulation.Results：在年轻的成年兔，最大血小板聚集，如预期的那样，减少了30 ± 4%，在CGS处理的等分试样与车辆控制。相比之下，来自4岁大的兔子的血液样品对A2受体刺激是难治的：在老年组中，用CGS处理没有引起血小板聚集的变化（与年龄匹配的载体对照相比降低2 ± 3%;与在年轻成年人中观察到的降低30%相比，p<0.01）。在大鼠模型中获得的数据是类似的，在兔子中看到的：最大血小板聚集减少了18 ± 5%与1 ± 7%与CGS治疗在年轻的成年人与衰老animals.Conclusion：我们的研究结果提供了novelin vitroevidence的年龄相关的损失，血小板对腺苷介导的“预处理”的反应。
Background: Brief preconditioning (PC) ischemia, in addition to its well-described cardioprotective effects, has been shown in some studies to act on circulating platelets and attenuate platelet adhesion and aggregation in models of unstable angina and acute myocardial infarction. This ‘anti-platelet’ effect of PC may be triggered by release of adenosine from ischemic/reperfused myocardium and activation of adenosine A2receptors on the platelets’ surface. However: (1) all current data on the platelet inhibitory effects of PC ischemia and A2receptor stimulation have been obtained in adult populations; and (2) there is evidence of age-associated alterations in myocardial adenosine release, receptor responsiveness and post-receptor signaling.Objective: Our aim was to evaluate, using an establishedin vitromodel of platelet aggregation and exogenous administration of an adenosine A2agonist, whether the favorable effects of adenosine A2receptor stimulation on platelet responsiveness are compromised in aging populations.Methods: Arterial blood samples were obtained from young adult versus old rabbits (6 months versus 4 years of age) and young adult versus senescent rats (4 months versus 2 years of age). Matched aliquots from each animal were randomly assigned to receive exogenous treatment with either the A2agonist CGS 21680 or vehicle. Maximum platelet aggregation was quantified by whole blood impedance aggregometry, using collagen as the aggregatory stimulus.Results: In young adult rabbits, maximum platelet aggregation was, as expected, reduced by 30 ± 4% in CGS-treated aliquots versus vehicle-controls. In contrast, blood samples from 4 year old rabbits were refractory to A2receptor stimulation: in the old cohort, treatment with CGS evoked no change in platelet aggregation (decrease of 2 ± 3% versus age-matched vehicle controls;p< .01 versus the decrease of 30% seen in young adults). Data obtained in the rat model were analogous to those seen in the rabbit: maximum platelet aggregation decreased by 18 ± 5% versus 1 ± 7% with CGS treatment in young adult versus senescent animals.Conclusion: Our results provide novelin vitroevidence of an age-associated loss in platelet responsiveness to adenosine-mediated ‘preconditioning’.