Bolus injections of novel thrombogenic site-targeted fusion proteins comprising annexin-V and Kunitz protease inhibitors attenuate intimal hyperplasia after balloon angioplasty.
Bolus injections of novel thrombogenic site-targeted fusion proteins comprising annexin-V and Kunitz protease inhibitors attenuate intimal hyperplasia after balloon angioplasty.
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DOI：
10.1016/j.ijcard.2017.03.150
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发表时间：
2017-08-01
影响因子：
3.5
通讯作者：
Chen WJ
中科院分区：
文献类型：
--
作者：
Yeh YH;Chang SH;Chen SY;Wen CJ;Wei FC;Tang R;Achilefu S;Wun TC;Chen WJ
实验动物血管成形术后全身给予常规抗血栓药物可减少新生内膜形成。然而，由于出血风险高，这些结果的临床转化尚未成功。我们试图确定新型膜联蛋白-V（ANV）-Kunitz蛋白酶抑制剂融合蛋白TAP-ANV和ANV-6L 15是否可以特异性靶向血管损伤部位并限制新生内膜形成，而不诱导大鼠颈动脉球囊血管成形术损伤模型中的全身低凝。在球囊损伤和注射荧光ANV或ANV-6L 15后进行近红外成像以检查它们的生物分布。对于围手术期治疗，TAP-ANV或ANV-6L 15静脉推注给药3次：球囊损伤前30分钟、术后即刻和球囊损伤后120分钟。对于延长治疗，在第-2天、第-3天和此后每隔一天进行额外静脉推注。在第7天和第14天收集颈动脉用于分析。采集血液用于测量凝血参数。近红外成像和免疫组化显示荧光ANV和ANV-6L 15特异性地定位于损伤的颈动脉，并且在24小时后显著量的ANV-6L 15仍然结合于损伤的动脉。围手术期注射TAP-ANV或ANV-6L 15导致内膜/中膜比率降低56%。两者的延长注射产生了类似的结果。两组均在球囊损伤后第7天降低PCNA的表达，第14天升高Calponin的表达。TAP-ANV和ANV-6L 15可以在静脉推注后特异性定位于球囊损伤的颈动脉，导致内膜增生的显著衰减，而不诱导全身低凝状态。
Systemic administrations of conventional antithrombotics reduce neointima formation after angioplasty in experimental animals. However, clinical translation of these results has not been successful due to high risk for bleeding. We sought to determine whether novel annexin-V (ANV)-Kunitz protease inhibitor fusion proteins, TAP-ANV and ANV-6L15, can specifically target to vascular injury site and limit neointima formation without inducing systemic hypo-coagulation in a rat carotid artery balloon angioplasty injury model. Near infrared imaging was carried out after balloon-injury and injection of fluorescent ANV or ANV-6L15 to examine their bio-distributions. For peri-procedure treatment, TAP-ANV or ANV-6L15 was administered as i.v. boluses 3 times: 30-minutes before balloon-injury, immediate after procedure, and 120-minutes postballoon-injury. For extended treatment, additional i.v. bolus injection was given on day-2, day-3 and every other day thereafter. Carotid arteries were collected on day-7 and day-14 for analysis. Blood was collected for measurement of clotting parameters. Near infrared imaging and immunochemistry showed that fluorescent ANV and ANV-6L15 specifically localized to injured carotid artery and significant amount of ANV-6L15 remained bound to the injured artery after 24-h. Peri-procedure injections of TAP-ANV or ANV-6L15 resulted in decrease of intima/media ratio by 56%. Extended injections of both yielded similar results. Both decreased the expression of PCNA on day-7 and increased the expression calponin on day-14 in the intima post-balloon-injury. TAP-ANV and ANV-6L15 can specifically localize to balloon injured carotid arteries after i.v. bolus injections, resulting in substantial attenuation of intimal hyperplasia without inducing a state of systemic hypo-coagulation.
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DOI：
10.1016/s0735-1097(96)00362-2
发表时间：
1996-12-01
影响因子：
24
作者：
Abendschein, DR;Recchia, D;Eisenberg, PR
通讯作者：
Eisenberg, PR
影响因子：
5.8
作者：
Draeger, Annette;Monastyrskaya, Katia;Babiychuk, Eduard B.
通讯作者：
Babiychuk, Eduard B.
影响因子：
3.6
作者：
Lee, Hyeran;Mason, J. Christian;Achilefu, Samuel
通讯作者：
Achilefu, Samuel
影响因子：
16.6
作者：
Bouter A;Gounou C;Bérat R;Tan S;Gallois B;Granier T;d'Estaintot BL;Pöschl E;Brachvogel B;Brisson AR
通讯作者：
Brisson AR
影响因子：
6.7
作者：
Asada, Y;Hara, S;Sumiyoshi, A
通讯作者：
Sumiyoshi, A