Transcoronary Concentration Gradients of Circulating MicroRNAs
Transcoronary Concentration Gradients of Circulating MicroRNAs
复制标题
DOI：
10.1161/circulationaha.111.037572
复制
发表时间：
2011-11-01
期刊：
影响因子：
37.8
通讯作者：
Zeiher, Andreas M.
中科院分区：
文献类型：
--
作者：
De Rosa, Salvatore;Fichtlscherer, Stephan;Zeiher, Andreas M.
循环中microRNA（miR）水平已被提议作为心血管疾病的生物标志物。为了确定心脏作为释放到循环中的miR的潜在来源，我们测量了肌肉富集的miR在冠状动脉循环中的浓度梯度。（miR-133a、miR-499、miR-208a），血管（miR-126，miR-92a），白细胞相关（miR-155），方法和结果-通过TaqMan聚合酶链反应在EDTA中测量循环miR-223。同时从无冠状动脉疾病患者（n = 7）、稳定型冠状动脉疾病患者（n = 31）和肌钙蛋白阳性急性冠状动脉综合征患者（n = 19）的主动脉和冠状静脉窦获得血浆。肌钙蛋白阳性的急性冠状动脉综合征患者与冠状动脉疾病患者相比，其主动脉中肌肉富集的miR-499（> 20倍; P <0.01）、miR-133a（11倍; P <0.01）和miR-208a（5倍; P <0.01）的循环水平显著升高。重要的是，在肌钙蛋白阳性的急性冠状动脉综合征患者的冠状动脉循环中，miR-499和miR-133a的循环水平显著增加，表明心肌损伤期间释放到冠状动脉循环中。事实上，miR-499浓度梯度与高敏肌钙蛋白T测量的心肌损伤程度显著相关（r = 0.70，P <0.01）。相比之下，循环水平的miR-126（P = 0.16）减少，在transcoronary passage.Conclusions，肌肉富集的miR-499和miR-133a从心脏释放到冠状动脉循环心肌损伤的证据，心肌损伤的患者在transcoronary passage.Conclusions消耗，而血管miR-126消耗在transcoronary passage.Conclusions。循环miR在经冠状动脉通过过程中的差异调节可能为开发其作为心脏生物标志物的作用提供重要的见解。
Background-Circulating levels of microRNA (miR) have been proposed as biomarkers for cardiovascular disease. To identify the heart as a potential source for miRs released into the circulation, we measured concentration gradients across the coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular (miR-126, miR-92a), leukocyte-related (miR-155), and platelet-enriched (miR-223) miRs.Methods and Results-Circulating miRs were measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the aorta and the coronary venous sinus in patients without coronary artery disease (n = 7), with stable coronary artery disease (n = 31), and with troponin-positive acute coronary syndromes (n = 19). Circulating levels of the muscle-enriched miR-499 (>20-fold; P < 0.01), miR-133a (11-fold; P < 0.01), and miR-208a (5-fold; P < 0.01) were significantly elevated in the aorta of troponin-positive acute coronary syndrome patients compared with patients with coronary artery disease. Importantly, there was a significant increase in circulating levels of miR-499 and miR-133a across the coronary circulation in troponin-positive acute coronary syndrome patients, suggestive of a release into the coronary circulation during myocardial injury. Indeed, miR-499 concentration gradients were significantly correlated with the extent of myocardial damage as measured by high-sensitivity troponin T (r = 0.70, P < 0.01). In contrast, circulating levels of miR-126 (P = 0.16) decreased during transcoronary passage in patients with evidence of myocardial injury, suggesting consumption during transcoronary passage.Conclusions-Muscle-enriched miR-499 and miR-133a are released from the heart into the coronary circulation on myocardial injury, whereas the vascular miR-126 is consumed during transcoronary passage. The differential regulation of circulating miRs during the transcoronary passage might provide important insights to exploit their role as cardiac biomarkers.