Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load.
Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load.
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DOI：
10.1016/j.jacc.2008.09.027
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发表时间：
2008-12-16
影响因子：
24
通讯作者：
Joseph, Lija
中科院分区：
文献类型：
--
作者：
Bartunek, Jozef;Delrue, Leen;Van Durme, Frederik;Muller, Olivier;Casselman, Filip;De Wiest, Bart;Croes, Romaric;Verstreken, Sofie;Goethals, Marc;de Raedt, Herbert;Weinberg, Ellen O.;Vanderheyden, Marc;Sarma, Jaydeep;Joseph, Lija
目的是探讨1)血清ST2水平与血流动力学/神经激素变量的关系；2)心肌ST2生成；3)左室压过负荷合并充血性心肌病患者心肌、内皮和白细胞中ST2、膜锚定ST2L及其配体IL-33的表达。心衰时血清ST2水平升高。ST2与血流动力学变量的关系、ST2的来源以及ST2L和IL-33在心血管系统中的表达尚不清楚。检测左室肥厚（主动脉瓣狭窄，AS， N=45）、充血性心肌病（CCM， N=53）和对照组（N=23）患者的血清ST2 （pg/mL，中位数[25 -75]）。ST2与NT-pro BNP、CRP及血流动力学指标相关。冠状窦和动脉血取样测定心肌ST2梯度（产生）。采用RT-PCR法检测心肌组织和白细胞中ST2、ST2L、IL-33的表达；在人内皮细胞中评估ST2蛋白的产生。IL-33蛋白在冠状动脉内皮的表达（免疫组化）与对照组（49[4-89]）相比，AS （103[65-165], p<0.05）和CCM (194[69-551], p<0.01) ST2升高，并与BNP （r=0.5, p<0.05）、CRP （r=0.6, p<0.01）和LV EDP （r=0.38, p<0.03）相关。与对照组相比，AS和CCM的LV ST2 mRNA相似。心肌未见ST2蛋白梯度。内皮细胞分泌ST2。IL-33蛋白在冠状动脉内皮中表达。白细胞ST2L与IL-33水平高度相关（r=0.97, p<0.001）。在高血压和心力衰竭患者中，血清ST2与舒张负荷相关。虽然心脏、内皮和白细胞表达ST2/ST2L/IL-33通路的成分，但循环血清ST2的来源是心肌外。
Aims were to investigate 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; 3) expression of ST2, membrane-anchored ST2L, and its ligand, IL-33, in myocardium, endothelium and leukocytes from patients with LV pressure overload and congestive cardiomyopathy. Serum levels of ST2 are elevated in heart failure. Relationship of ST2 with hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown. Serum ST2 (pg/mL; median [25th-75th]) was measured in patients with LV hypertrophy (aortic stenosis, AS, N=45), congestive cardiomyopathy (CCM N=53), and Controls (N=23). ST2 was correlated to NT-pro BNP, CRP and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. ST2, ST2L and IL-33 were measured (RT-PCR) in myocardial biopsies and leukocytes; ST2 protein production was evaluated in human endothelial cells. IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium ST2 was elevated in AS (103[65-165], p<0.05) and CCM (194[69-551], p<0.01) vs. Controls (49[4-89]) and correlated with BNP (r=0.5; p<0.05), CRP (r=0.6; p<0.01) and LV EDP (r=0.38, p<0.03). LV ST2 mRNA was similar in AS and CCM vs. Control (NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r=0.97, p<0.001). In human hypertrohy and failure, serum ST2 correlates with diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.
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DOI：
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发表时间：
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影响因子：
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