Optimal reactive oxygen species concentration and p38 MAP kinase are required for coronary collateral growth
Optimal reactive oxygen species concentration and p38 MAP kinase are required for coronary collateral growth
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DOI：
10.1152/ajpheart.01330.2006
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Chilian, William M.
中科院分区：
文献类型：
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作者：
Rocic, Petra;Kolz, Christopher;Chilian, William M.
活性氧（ROS）与冠状动脉侧支生长（CCG）有关。我们评估了人冠状动脉内皮细胞（HCAEC）形成管腔对ROS的需求。体内CCG和ROS刺激血管生长的信号转导（p38 MAP激酶）。含黄素氧化酶抑制剂二苯基碘鎓（DPI）或超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸酯（DETC）阻断血管内皮生长因子诱导的HCAEC管形成在基质胶。我们评估了DPI和DETC油CCG在重复缺血（RI）大鼠模型中的作用（每20 min阻断冠状动脉左前降支40 s，持续2 h 20 min，3次/d，10 d）。DPI或DETC腹腔注射，或在饮用水中给予NAD（P）H氧化酶抑制剂夹竹桃苷。侧支依赖性血流（通过使用微球测量）表示为正常和缺血区血流的比率。在假手术大鼠中，缺血区的侧支血流为正常区的18 +/- 6%，在RI组中。缺血区的侧支血流为正常区的83 ± 5%。DPI防止RI后侧支血流增加（正常区的25 +/- 4%）。RI后用夹竹桃麻素获得类似的结果（正常区的32 +/- 7%）。DETC获得了相似的结果（RI后侧支血流为正常区的21 +/- 2%）。DPI和DETC阻断RI诱导的p38 MAP激酶激活对血管内皮生长因子和RI的反应。这些结果证明了在HCAEC管形成中需要最佳ROS浓度。CCG和p38 MAP激酶激活。p38 MAP激酶抑制阻止HCAEC管形成并部分阻断RI诱导的CCG（正常区流量的42 +/-7%），表明p38 MAP激酶是CCG的关键信号介质。
Reactive oxygen species (ROS) Lire implicated in coronary collateral growth (CCG). We evaluated the requirement for ROS ill human coronary artery endothelial cell (HCAEC) tube formation. CCG in vivo, and signaling (p38 MAP kinase) by which ROS May Stimulate vascular growth. The flavin-containing oxidase inhibitor diphenyleneiodonium (DPI) or the superoxide dismutase inhibitor diethyldithiocarbamate (DETC) blocked vascular endothelial growth factor-induced HCAEC tube formation in Matrigel. We assessed the effect of DPI and DETC oil CCG in a rat model of repetitive ischemia (RI) (40 s left anterior descending coronary artery occlusion every 20 min for 2 h 20 min, 3 times/day, 10 days). DPI or DETC was given intraperitoneally, or the NAD(P)H oxidase inhibitor apocynin was given in drinking water. Collateral-dependent flow (measured by using microspheres) was expressed as a ratio of normal and ischemic zone flows. In sham-operated rats, collateral flow in the ischemic zone was 18 +/- 6% of normal zone, in the RI group. collateral flow in the ischemic zone was 83 +/- 5% of normal zone. DPI prevented the increase in collateral flow after RI (25 +/- 4% of normal zone). Similar results were obtained with apocynin following RI (32 +/- 7% of that in the normal zone). DETC achieved similar results (collateral flow after RI was 21 +/- 2% of normal zone). DPI and DETC blocked RI-induced p38 MAP kinase activation in response to vascular endothelial growth factor and RI. These results demonstrate a requirement for optimal ROS concentration in HCAEC tube formation. CCG, and p38 MAP kinase activation. p38 MAP kinase inhibition prevented HCAEC tube formation and partially blocked RI-induced CCG (42 +/- 7% of normal zone flow), indicating that p38 MAP kinase is a critical signaling mediator of CCG.